In this episode, Bethany and Molly focus on obstetricians and other medical professionals who play the critical role of diagnosis and initial treatment planning for alloimmunized patients.
In this episode, Bethany and Molly focus on obstetricians and other medical professionals who play the critical role of diagnosis and initial treatment planning for alloimmunized patients. To close, Bethany and Molly play a game to try to treatment plan for alloimmunized patients based on limited information, and find a new level of appreciation for physicians.
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Reference
Research for this episode provided by Bethany Weathersby and Molly Sherwood of the Allo Hope Foundation. Find more information at https://allohopefoundation.org
The Allo Podcast is produced and edited by Media Club
Molly Sherwood:
The information shared on The Allo Podcast is not intended as medical advice. Your medical care decisions should be made in consultation with your physician who is familiar with your specific case.
Bethany Weathersby:
Hi. Welcome to The Allo Podcast from the Allo Hope Foundation. I'm Bethany Weathersby.
Molly Sherwood:
And I'm Molly Sherwood. And we're ready to roll today.
Bethany Weathersby:
Here we go.
Molly Sherwood:
It's weird being virtual. Well, not virtual, I guess we are virtual from each other, but now that we've met, we finally met in person. And now I feel like I can imagine your whole self in your office now.
Bethany Weathersby:
Yes. I know. That was really fun. I already am thinking about the hilarious things that you said, and I really want to share them here.
Molly Sherwood:
Oh, gosh. What did I say?
Bethany Weathersby:
Okay. When you know someone well, virtually, it's very slightly bizarre to meet them in person because-
Molly Sherwood:
Yeah, I was a little worried. Well, I mean, like worried. I don't know.
Bethany Weathersby:
It's just weird because we know each other well, and we have a wonderful friendship and relationship, but we've never seen each other in real life. I feel like I'm a large gal.
Molly Sherwood:
Yeah, you are.
Bethany Weathersby:
Yeah.
Molly Sherwood:
Just your appendages are large.
Bethany Weathersby:
Exactly.
Molly Sherwood:
Your wingspan is large.
Bethany Weathersby:
Exactly. And you are a very tiny person. You are a small, fragile person physically, not mentally or emotionally.
Molly Sherwood:
Yeah, I know. Thank you. Thank you.
Bethany Weathersby:
That was hilarious. I was like, "Oh, you're so tiny." And you're like-
Molly Sherwood:
"Oh, you're a tiny toothpick that I might accidentally snap."
Bethany Weathersby:
Yeah, I'm huge.
Molly Sherwood:
Well, you just have big hands and big feet.
Bethany Weathersby:
Exactly.
Molly Sherwood:
You showed me your legs, and you were standing there and you're not that tall. You're not that tall. You're average height.
Bethany Weathersby:
No.
Molly Sherwood:
You showed me your wingspan.
Bethany Weathersby:
You are average height, I think.
Molly Sherwood:
Okay. I'm 5"6', you're 5"8'.
Bethany Weathersby:
I'm 5"8'. Okay. So maybe I'm little above average height.
Molly Sherwood:
But then when you showed me your wingspan, that's when I was like, wow, wait a minute. You're actually ... I was like, you're actually small. You're small. What did I say?
Bethany Weathersby:
You said, "You're short for the size of your," and then you took a long pause.
Molly Sherwood:
Well, I didn't take a long pause. You just interrupted me to start laughing.
Bethany Weathersby:
Okay. But you were going to say the size of your appendages.
Molly Sherwood:
Yes, exactly. You're fairly tall for a woman.
Bethany Weathersby:
Okay, yes.
Molly Sherwood:
But actually for the ratio of your arm length and your hands and feet, you're actually short, which I wasn't expecting.
Bethany Weathersby:
Exactly. Right. So that was new. And then 10 minutes later, we were just comparing our C-section scars.
Molly Sherwood:
Yeah, we were. We just jumped right in.
Bethany Weathersby:
We felt very comfortable. It was great. It was really fun. Okay, so let's turn our attention to the topic today, which I'm really excited about.
Molly Sherwood:
I don't know how long we were planning to do this topic, but it kind of presented itself because we were getting ready to go to the big annual meeting for American OBs. It's called ACOG. By the time this airs, the meeting will already be over, but it happens every year. Anyway, we were working on what materials we're going to send, and what our banners going to be, and what our handouts are going to be. That's when we realized that there's unique messaging that we want to deliver to OBs specifically.
Bethany Weathersby:
It was kind of a light bulb moment for me as we were preparing the materials for ACOG. I always knew that OBs are very important when it comes to this disease, but it just made me really focus on them and I realized how incredibly vital their role is in the management of an alloimmunized pregnancy. I think we haven't really given them the credit or the attention that they deserve. Hopefully, we can do that with this episode. Yeah, they're usually the ones giving the patient the news about her diagnosis of maternal alloimmunization.
Molly Sherwood:
The way a woman finds out this disease has a serious impact on the way she emotionally processes and copes and prepares for the rest of her pregnancy.
Bethany Weathersby:
Yeah. The way that OB delivers that news and explains the condition initially really does set the stage for the rest of the woman's pregnancy, and the rest of her experience with this condition, however many pregnancies that is. Not only does the OB impact the way the patient processes the news of the diagnosis, but he or she also has the power to set both patients, because they do have two patients, the mom and the baby up for the very best possible outcome. That involves the initial blood work that will show how much risk the baby might be in and how urgently they need to refer that patient to an MFM or if they need to at all. And probably most importantly, who to refer the patient to, which maternal fetal medicine specialist. If you look at the story we just heard from Brittany, it's just a very stark reminder of how important that referral is from the OB and getting set up for the right care for an allo pregnancy.
Molly Sherwood:
Mm-hmm. That's so true. I think when we were reflecting on overall the purpose of this episode, we both believe wholeheartedly that improving awareness of this condition amongst OBs will have a huge impact, not only on the woman's mental health, but it can have a direct impact on the fetal outcomes. Because getting the baby to the right doctor, not just the closest doctor on time, can truly be the difference between life and death.
Bethany Weathersby:
Yeah, yeah. Okay. Let's give these OBs the attention they deserve. In this episode, we will talk about that initial diagnosis and what a patient wants to hear from her OB, and then we'll also go through the most important blood tests that OBs can order to assess the level of risk and figure out how quickly the patient should be seen by a high risk doctor, an MFM. And then, let's spend a little time discussing how important it is for the OB to choose the right MFM to refer to.
Molly Sherwood:
Also, we have a fun game at the end of this episode, which I'm so excited about.
Bethany Weathersby:
Oh, yeah.
Molly Sherwood:
Yeah, it's going to be good. Actually, I'm most excited for that. I think it's going to be really fun.
Bethany Weathersby:
Me, too.
Molly Sherwood:
At least for us, maybe we're just nerds, but-
Bethany Weathersby:
I think we are.
Molly Sherwood:
That's fine.
Bethany Weathersby:
That's fine. Yeah, we'll be nerds having fun.
Molly Sherwood:
Yeah, that's fine.
Bethany Weathersby:
Okay.
Molly Sherwood:
Okay. Let's start with what your alloimmunized patient wants to hear from you. In the US, at least and most other developed countries, screening for antibodies in the first trimester is standard. It's part of your first trimester blood work. In underdeveloped countries, it may not happen until someone has already had an affected baby or lost a baby to HDFN. But in any case, once a positive antibody screen comes up, most labs will automatically try to identify the antibody, and then get a titer on that antibody.
Bethany Weathersby:
Mm-hmm. Right, and if they don't identify the antibody and get a titer automatically, it needs to be ordered as soon as possible because that's critical initial information that the OB and the patients really need to know upfront.
Molly Sherwood:
Yeah, because a really high titer could mean that something needs to happen right now. One of my favorite working world phrases is, "Do not bring problems, bring solutions." I think that in my head all the time.
Bethany Weathersby:
I could see that.
Molly Sherwood:
Yeah. I'm like, I'm not going to complain about this thing until I also am presenting a solution to this thing.
Bethany Weathersby:
Yeah. That's why you're so efficient.
Molly Sherwood:
I love efficiency. It's my favorite thing.
Bethany Weathersby:
I know. You're really good at it.
Molly Sherwood:
It's ideal for an OB to bring the news to their patient and already be ready to share the antibody, and the titer, and the plan.
Bethany Weathersby:
At some point in that delivery of this diagnosis, it would be great for them to give a basic explanation of what's going on. I know that it is a very complex and rare disease, and so that is hard. But hopefully, we can help get the resources out there so that this can be a smooth delivery of this diagnosis.
Molly Sherwood:
Yeah, exactly. I'm just trying to be pregnant, have a normal day, get back in time to put my kids down for their naps. And then you're throwing a bunch of jargon at me. I'm totally caught off guard. I'm probably going to remember 10% what they're saying. So I think it's really helpful for the OBs to know ahead of time what they will say when they're delivering this news to their patients.
Bethany Weathersby:
You are married to a medical professional, so I don't know if you've heard this, and maybe your husband is never in this position, hopefully, but when they are giving the news of something tragic, like a death to a family member or a loved one, they're supposed to use straightforward language. They shouldn't say, "I'm so sorry, but your father's no longer with us," or "Your wife didn't make it," like didn't make it to the hospital yet or what? When you're in that position as the person receiving the news, it's just completely overwhelming. They're supposed to say, "Your father died. I'm so sorry." Just straightforward.
Molly Sherwood:
This is getting morbid, but yes.
Bethany Weathersby:
It is. But don't worry, there's a light at the end of the tunnel. And being vague and reassuring is not actually reassuring to us as mothers, right?
Molly Sherwood:
Such a good point. Such a good point. Yeah, that's really true. Okay, so let's pretend you go back in time to the day you were diagnosed.
Bethany Weathersby:
Oh, no. Do we really have to?
Molly Sherwood:
Sorry. [inaudible]
Bethany Weathersby:
Let's do it.
Molly Sherwood:
All right, this is what I want to know from you. If you could write a script for the exact words you want your OB to say when he gives you your diagnosis, what would it be?
Bethany Weathersby:
Okay. In hindsight, I can think this through at the time. I wouldn't expect him to know all these things, but let's just say, we can go back in time and change it. Okay. I'll set the scene. I'm the doctor. I'm a very tall, middle-aged man with my white coat on. I have my clipboard and my kind, I have my kind eyes, my nice smelling cologne.
Molly Sherwood:
Oh, okay. We're getting specific.
Bethany Weathersby:
I'm very gentle and intelligent. Okay. I'd probably say something like, "Congratulations, I just saw the ultrasound report and your baby looks beautiful, measuring right on track with a great heartbeat. It's just what we want to see. First I want to talk about the blood work that we did at your six week check-in, and that's just the routine blood work that we do to check for several things to make sure you have a safe pregnancy. Actually-"
Molly Sherwood:
By the way, I'm glad you said that because I feel like a lot of women don't even realize they had that blood work.
Bethany Weathersby:
Right.
Molly Sherwood:
They just go get that blood work done and they don't know what it was for. Anyway, go on.
Bethany Weathersby:
Exactly. Yeah, I had no idea. "One of the things that we look for is red cell antibodies, and your test actually came back positive. So the results show that you have something called anti-Kell antibodies, and these antibodies are not dangerous to you at all, but there is a possibility that they could cause some risks for your baby later in the pregnancy. Right now, there's no risk. Your baby's totally fine. And before I go on, I want to say that having these antibodies does not mean that you can't have a healthy baby."
"It means you'll probably have more blood tests and ultrasounds, more appointments, and it might take more work in general and a team effort to get this baby here, especially compared to your last two pregnancies that were very smooth. But this is a treatable and temporary condition for your baby. And when you test positive for anti-Kell antibodies, it means you have something called maternal alloimmunization, which is just a very natural immune response that your body has had because you were exposed to a blood type that's different from your own." And then I would give a whole spiel, just a very basic overview like we do on our website of what's happening. And then honestly, I would want my doctor to write down the name of my condition.
Molly Sherwood:
It's such a good idea, yes.
Bethany Weathersby:
Give it to me. Anti-Kell antibodies, maternal alloimmunization, hemolytic disease of the fetus and newborn. I know at the time, it didn't exist, but I would love for him to hand me the Allo Hope Foundation patient booklets that gives very thorough explanation of everything, what to expect, what tests should be run. That would've helped so much. And then of course, I would want him to share any information that he had with me about my tests. So he did know at the time, my titer, and so I wish he had given me the titer and just said, "The titer tells us how much antibodies in your blood and helps us know the best way to monitor and treat if needed."
And then of course, like you said, Molly, just give a plan of where we go from there. I know that that takes time on the OB's part and more effort and planning ahead of time, but it is so, so vital for us as patients, and it makes a huge difference for the entire pregnancy, honestly. One last thing I want to add is a lot of doctors say, "Don't google this. Don't google it." And I think it's really wonderful when the doctor encourages the patient to do whatever research she wants to do on the condition, because that's empowering to us. The more information we have, I think the more equipped we feel and we are capable of knowing like, "I don't feel good reading horror stories, so I'm not going to." We can do that. I think some of the worst advice that they can give is "Don't google this. Don't research this on the internet."
Molly Sherwood:
Right, right.
Bethany Weathersby:
That's literally what saved my children's lives.
Molly Sherwood:
Yes. And you know what else I would love for an OB to say at this point? I would love if they acknowledge the extreme burden this disease puts on mothers. Remember going back to our questionnaire study, they were totally mind blowing in terms of the percentage of women who report feelings of isolation, depression, anxiety. But anyway, I'm sure I'll share that more. But just to sum it up, so when we talked about those same women, those 127 women in our study, and they had to rate the emotional burden of their alloimmunized pregnancy from 1 to 10, least burdensome to most burdensome, 87% gave a rating of five or greater, which is ridiculous. And guess what? 35% gave a rating of 10, 10 out of 10.
Bethany Weathersby:
Wow.
Molly Sherwood:
That's crazy. Think about how often someone asks you to rate something on a scale, how often do you actually just say 10 out of 10? It's so rare, because you feel like, "Let me save that for the most extreme situation ever." But that many women are saying 10 out of 10.
Bethany Weathersby:
Those are really sobering statistics. I mean, not surprising because we've been through it, but it is very sobering to think about. As I'm thinking back to my OB and what could he have said to prepare me for the devastating consequences emotionally that this disease would have on me, I don't know. I think that just having him acknowledge how hard it can be to get this diagnosis is helpful, and he did. Remember I said he had kind eyes, he really did. And that was very helpful, and I felt supported even if I didn't get the right information. I felt safe in his presence, and that's really important. I do think that connecting the patient to other alloimmunized moms is a huge step in the right direction when it comes to emotional support. Another thought is that the OB does actually have the power to lessen the impact of alloimmunization on the mother by providing the right care that her baby needs to stay safe, and especially during those first few crucial weeks of pregnancy.
Molly Sherwood:
Yeah, I agree. This is the perfect shift into our next bucket that we wanted to talk about today, which is, I kind of call it triaging your alloimmunized patient. What do we do right away when we figured out the patient has this disease? How do we triage her and figure out what's next for her and figure out the urgency?
Bethany Weathersby:
Yeah. I think triage is such a great word because, and that's part of why it's hard. They're getting all these patients, and so they have to make these very crucial time-sensitive decisions on what each person needs. And they all come with varying levels of urgency. Yeah, they really do have to look at this situation and know, "Okay, this is pretty serious. This is time-sensitive."
Molly Sherwood:
Yeah. And before we dive in, I want to reinforce that the timing of all of this is super important. The blood tests, the referrals, and some treatments for HDFN are time sensitive. We've talked about with severe disease plasmapheresis and IVIG is best started at 10 to 12 weeks. They're only going to be successful if they're done at the right time, and some women even need IUTs earlier than they may be traditionally sent to the MFM. They may not see an MFM until 18 or 20 or 22 weeks, but they needed an IUT at 16 or 17 weeks. So, having it done at the right time and in the right order is super important.
Bethany Weathersby:
Yeah, that's a really good point. Let's try to be really mindful of that as we talk through what the care should look like. We will try to point out the timing and order of everything as we talk through this. Also a quick reminder that when the OB provides care with that timing in mind, then that greatly eases the emotional burden for the mother because she doesn't feel like she has to advocate and do it quickly and do it in time. If the OB is taking care of it, she can relax in that care.
Molly Sherwood:
Right, and figuring out that urgency, I guess. Now, we're talking about how to do the risk assessment. Once the antibody is identified, you'll want to make sure that this antibody is known to cause HDFN, because some don't cross the placenta and don't pose any risk. There's a table in the ACOG practice bulletin for alloimmunization, which I'm sure any OB would be very familiar with, but we'll link it in the show notes anyway.
Bethany Weathersby:
Right. Okay. So if the antibody is one that can cause HDFN, then the next step is to look at the antibody titer, which we mentioned earlier and you want to distinguish right off the bat if that titer is critical or not. That's the whole purpose of looking at the titer. A critical titer means there are enough antibodies in the mother to possibly cause fetal anemia, which means the baby might end up needing in utero intervention and closer monitoring during the pregnancy. We consider a critical titer for all antibodies besides Kell to be 16. An exception to this is if the woman has a previous pregnancy that was affected by alloimmunization or if she had a previous titer of 16 or above, even if right now that titer is lower, that's still considered critical. Kell antibodies are known to be more aggressive because they suppress red cell production in addition to killing off the baby's existing red blood cells. So, any titer for Kell is considered critical.
Molly Sherwood:
Yeah. At this point, it's time to get the ball rolling. See the MFM, at least for a consult, and keeping that timeline in mind, this is one of those things that's super time sensitive. Even with a low titer, seeing the MFM and establishing care by 18 weeks is step one for a low titer pregnancy. Now, if the woman already has a critical titer, seeing an MFM by even 15 weeks is important because that's when MCA Doppler scans can begin in order to monitor for anemia. There are exceptions to this timeline, which I already alluded to with super severe disease, and we'll get back to that.
But once your OB gets your referral in for the MFM, it's also a good idea to go ahead and start figuring out the baby's antigen status, because the mom could have a titer in the thousands, but if the baby does not have the matching antigen that corresponds to her antibodies, then the baby won't be affected at all. But in any case, we just say, go ahead and get the ball rolling with referral to MFM, and then while you're waiting, you can turn to assessing the baby's antigen status. Do you want to walk through how we do that?
Bethany Weathersby:
Sure. Okay. The first thing that usually happens is looking at the dad, looking at the baby's father. He needs to be tested to see if he has the matching antigen, which the mother's antibodies could attack. The dad should have a blood draw and the test is called an antigen phenotype.
Molly Sherwood:
Yeah, not an antibody screen. That happens all the time.
Bethany Weathersby:
Exactly.
Molly Sherwood:
Antigen.
Bethany Weathersby:
We got to be so attentive to details.
Molly Sherwood:
Yes. Dad has the antigen, dad has the antigen.
Bethany Weathersby:
Right.
Molly Sherwood:
Mom has antibodies. Okay.
Bethany Weathersby:
All right. And that will let you know if it's possible for the baby to inherit that antigen from the dad. We did cover this in a lot more detail in our prenatal blood test episode in the first season.
Molly Sherwood:
Yeah, and the OB can order this test. A lot of times, there's this diffusion of responsibility thing going on where everyone is pointing to each other to order the test. We have patients being like, "Who am I supposed to ask for this test?" Because it's weird that it's a test on the dad, but it's just a simple lab that the OB can order. For me, my OB ordered it and my husband just went to a LabCorp and just had it drawn. Then, those results tell you if the father carries zero copies of the antigen, one copy, or two copies. We call that being homozygous or heterozygous. Without going into too much detail that we've already covered in the past, if the dad is homozygous, then you know that he has two copies of the antigen that is affected or that triggers the antibody response, so you know the baby's going to inherit that.
For an anti-Kell pregnancy, if the dad is homozygous and he has two copies of the big K antigen, you know the baby is going to inherit that and be affected. If the dad has two copies of the little K antigen, you are good to go because there's no way the baby can inherit the big K from their dad. The tricky part gets to, if the dad is heterozygous, meaning he has one copy of big K and one copy of little K because you don't know what the baby will inherit. Do you want to go over what to do then in that heterozygous situation?
Bethany Weathersby:
Sure. If you have a father who's heterozygous for the antigen, then it's important to try to figure out if the baby has that antigen or not, because it could go one of two ways. The baby could have it or the baby could not. The way that you do that is by ordering a cell-free fetal DNA test on the mom's blood. And that actually looks for fetal DNA circulating in the mother's blood to test the actual DNA of the baby, which is so cool that they can do that. This test is only possible for some antigens, D, C, K, E and Duffy through the unity screen in the US or Sanquin Labs in the Netherlands, although I'm not sure if they can do the Duffy antigen there. Another option is for the MFM and the patient to discuss together and decide if they just want to do a watch and wait approach to it.
Molly Sherwood:
Which is only okay if the titter is not critical, I would say. Do you think?
Bethany Weathersby:
Well, if it's critical, they just have to treat it as if the baby's positive.
Molly Sherwood:
Yes, yes, you're right. So treat it as if it's positive, right?
Bethany Weathersby:
Yeah. And then another option, which is the last option in our opinion, is the amniocentesis, which does come with risks even though they're pretty minimal chance of it happening. But it does come with risks. Okay. Finding out what the baby's antigen status is, is important. But before diving into that, you need to look at how far along the mother is in her pregnancy, what gestation is she at? If she has a critical titer and she's about, what would we say, 16 to 18 weeks, then you don't need to be waiting for the baby's antigen test to come back to start-
Molly Sherwood:
[Inaudible]
Bethany Weathersby:
Right. You got to start those MCA Doppler scans to monitor it for fetal anemia, because that's part of the timeline of this HDFN is you need to start monitoring. And then, if you find out the baby's antigen negative, you can stop, if that's what you decide to do.
Molly Sherwood:
Also, let's talk about that super special case that we were referring to earlier that requires a lot of fast movement, and that's a super high titer or a history of severe disease. If a mom has lost a child already to the disease, if their titer is really high and no one can really decide what we call really high, some people say it's 1024, 512, even 256, if their previous affected pregnancy had IUTs that started really early before 24 weeks, in those cases, the patient might be a candidate for plasmapheresis and IVIG, which is what we talked about in our severe disease episode, but that is best started at 10 to 12 weeks. So that's the kicker.
If the OB, it's kind of tricky because the OB needs to identify, "Man, this might need to happen now." If they think that this mom could have any chance of being a candidate for IVI G or plasmapheresis, that mom needs to go to the MFM tomorrow. Sometimes women even start their IVIG and plasmapheresis before they get their cell-free DNA testing back to even determine if the baby is affected. And if the baby comes back unaffected, then you just stop doing it and it's no harm, no foul, you know.
Bethany Weathersby:
Yeah, yeah. I'll just give an example. In my case, I had the initial antibody screen at six weeks. So when that blood work came back, those results came back, I had Kell with a titer of 1,024. If my OB had immediately got me in sooner for an appointment, referred me to the MFM-
Molly Sherwood:
The right MFM.
Bethany Weathersby:
The right MFM, exactly, then we would've had time to start plasmapheresis and IVIG, which my children needed to survive. Just seeing that Kell titer in the thousands should have been extreme warning, warning, warning, tornado siren, all the lights flashing saying, get her triage. Here we are, the most extreme situation. Get her to the right MFM as soon as possible. Since we're talking about the right MFM, let's move on to that piece, which I think is the most important piece, honestly. Just that referral to the right MFM and this disease has become so specialized, and it is rare.
Many MFMs don't have the chance to develop expertise in treatment and conducting intrauterine blood transfusions, which is the typical treatment for this disease. One way that an OB or a patient can figure out who the right MFM is or figure out what a certain MFM's experience level is, is by looking at the Allo Hope Foundation's Excellent Care Checklist that we have or you could listen back to our IUT episode and read those show notes because we put a lot of great questions in there for how to vet an MFM. Again, it's not that you're looking for a good MFM. There's a lot of really good MFMs who just haven't had an opportunity to get enough experience treating this disease.
Molly Sherwood:
I feel like you've seen time and time again how important this piece is. Can you just talk about some of the stuff you've seen in your pregnancies and just supporting other women? I know for me, in my allo pregnancies, I was seen at the only place in my state that treated the disease and the head of their blood bank said that they've only provided blood for IUTs three times in the last 15 years. That is not good. It's no one's fault, but-
Bethany Weathersby:
Where are those women going?
Molly Sherwood:
I don't know. I'm concerned. But anyway, it's no one's fault, but it just shows you how critical it's to see a doctor who sees these patients more often because treatment of this disease is, Dr. Moise has said this to us, it's an art. It requires a lot of experience and nuance and surgical skill.
Bethany Weathersby:
Right, right. As most of our listeners know, for me, finding the right MFM was the difference between life and death for my children. It wasn't the closest MFM, I think. The natural chain of events is that the referring physician goes to the closest qualified MFM. Correct?
Molly Sherwood:
Sure.
Bethany Weathersby:
In a lot of cases, that's not the right person for the patient. Sometimes it is. But yeah, it's really important to look at if they have experience doing intrauterine blood transfusions on a somewhat regular basis, and are they willing to collaborate with the experts for their patient's care? I think that's huge. A lot of patients do have their local MFM who then collaborates with usually one of the doctors on our medical advisory board or another expert in the field. Those usually turn out beautifully, wouldn't you say, Molly?
Molly Sherwood:
Oh, yeah.
Bethany Weathersby:
It's not uncommon that once a mom starts working with us and learning about what to look for, they do decide to travel out of state for their treatment. It feels like this extreme choice that you're making, but it's really not. For the safety and survival of your baby, you have to travel a little further, whether that's out of state or not. But that's pretty typical for this type of pregnancy because it is so specialized, it's so rare and nuanced. I think just to try to expect that as the referring OB and the patient is a good mindset.
Molly Sherwood:
Yeah, I agree. Going to those lengths aren't always required if the pregnancy doesn't end up needing IUTs, but the patient and the OB need to have a plan if they do need IUTs. Really, like we said, the MFM needs to be on board to refer if needed also in this situation where it's kind of low titer and nothing is acutely wrong right now.
Bethany Weathersby:
I'm going to say it again, even though we've said it a million times now, but that choice that the OB makes of who to refer their alloimmunized patient to for the MFM care is critical.
Molly Sherwood:
Yeah, I agree. Let's talk about, okay, this, we weren't even sure how or if we were going to talk about this piece because I don't think ... it's not that we disagree on it, we're just kind of-
Bethany Weathersby:
Unsure.
Molly Sherwood:
Okay. This topic, the topic is managing a low titer allo pregnancy and whether an OB can do it all the way to completion. Let's talk about the scenario where the OB could actually manage an allo pregnancy to delivery. Here's my perspective, and I did talk to Dr. Moise about this and he signed off on this thought, but I want to hear what you think, Bethany.
Bethany Weathersby:
Mm-hmm.
Molly Sherwood:
First, every allo pregnancy should have at least one MFM visit. They need to do that to establish care and be ready to ramp up at any time. But if titers are low and they stay below critical and there isn't a previously affected pregnancy, then I feel that they can be managed by an OB. Okay. There are of course logistical things that need to be considered. That would mean that the OB orders the titers every four weeks, and then every two weeks in the third trimester, and then they start antenatal testing at 32 weeks.
If the titers are still looking good, they can deliver their alloimmunized patient at 37 to 38 weeks just like recommended so long as they're in a hospital with a NICU that can handle typical allo issues like needing phototherapy, getting rapid results for labs, and being able to do a top-up transfusion, at least. So that 37 to 38 week delivery is often a point of contention with MFMs and OB-managed pregnancies. But we follow the ACOG's guidelines on late preterm/early term deliveries, and we'll put that in there. But basically that delivery time is there because maternal blood circulation increases a ton in the last month of pregnancy, and MCA scans aren't really accurate to see how the baby is doing. That's my piece on it. I'm trying to think ... Tell me what you think. Tell me what you think.
Bethany Weathersby:
Okay. Well, of course, you and I come from different backgrounds when it comes to experience with this disease.
Molly Sherwood:
Right.
Bethany Weathersby:
I always think worst case scenario.
Molly Sherwood:
Sure.
Bethany Weathersby:
I think, I do feel uneasy about it initially. I feel very uneasy about it. I think the fear behind that is that, would the titers be looked at often enough? And if the titter did rise quickly, could the patient get in quickly enough for an MCA Doppler scan and possible IUT with the MFM, would they be able to get them in quickly enough for that? Just because of the time-sensitive nature sometimes of the fetal anemia, which is very rare. I think if you have a super low titer, most of the time it doesn't shoot up quickly and you need a sudden IUT, wouldn't you say, Molly?
Molly Sherwood:
Yeah, I think I agree.
Bethany Weathersby:
Mm-hmm. I think if I was in that situation, I would feel comfortable as long as my OB was collaborating with an MFM throughout my pregnancy and totally down with that collaboration and communicating back and forth. Then, if my MFM could assure me that if I do need an MCA Doppler scan or an IUT, he could get me in quickly enough.
Molly Sherwood:
Yeah, I agree. So that's why I stand by, you still must see an MFM to establish care. Once you're their patient, in theory, if you are needed to be seen urgently, you should be able to be seen. But there's circumstances depending on where the woman lives, is the OB near the MFM, is the OB familiar with the MFM? Can they crosstalk enough? Would you be able to quickly switch to your MFM's location? Is that just too much of a logistical problem? In which case, maybe you commit to your MFM from the beginning.
Bethany Weathersby:
Right. One more thing I just remembered, I would want to make sure, if I was sticking with OB, would my OB be able to order that cell-free fetal DNA test for the baby's antigen status?
Molly Sherwood:
Yeah, that's a good point.
Bethany Weathersby:
Okay. I'm glad that you covered that portion because as you know, I have no idea what a low titer pregnancy is like.
Molly Sherwood:
I know.
Bethany Weathersby:
Yeah.
Molly Sherwood:
So that's my theory about it, and I think, yeah, I'm glad. I feel like we covered the bases with it. I feel like our listeners can just decide for themselves what makes the most sense given their location and access to other care.
Bethany Weathersby:
Molly, really quick, tell me if you, because you did have lower titer pregnancies than mine. Did your OB manage your pregnancies?
Molly Sherwood:
My OB managed my first one, but her office took so long to get the titers back. It took 10 days. I was like, okay, I'll let my OB manage me, but only if I can get my titers drawn at the MFMs, and then they would share. Lucky for me, the OB and MFM were five minutes from each other. So that worked for me.
Bethany Weathersby:
That's great.
Molly Sherwood:
Yeah. But that's a perfect example of how it's circumstantial.
Bethany Weathersby:
Yeah, and how well those two care providers collaborate, I think.
Molly Sherwood:
Right.
Bethany Weathersby:
Yeah. I think we got my main messages across, which is the right blood work, the right referral to the right MFM, and staying on top of the timing and acknowledging the heavy burden that this disease comes with from others. I think that really sets the stage for a well-managed alloimmunized pregnancy and really has a direct impact on outcomes.
Molly Sherwood:
Totally agree. Totally agree.
Bethany Weathersby:
Mm-hmm.
Molly Sherwood:
Okay, I want to do the fun part now. It's time for a game. It's going to be great. Let's tell them about our game. We're going to be the next Andy Cohen, do you watch Real Housewives?
Bethany Weathersby:
No. Girl, I don't have time to watch TV.
Molly Sherwood:
Okay. I love my Real Housewives. It's like my special veg time. Andy Cohen is the producer and he does this talk show every night afterwards, and they have the cheesiest most silly games.
Bethany Weathersby:
Oh, my gosh. I love it.
Molly Sherwood:
Anyway, I aspire to be him. So this is going to be us now.
Bethany Weathersby:
Okay. I have a treat for you then. All right. This is going to be a Q&A segment where we asked other members of our team to draft up questions that we thought would be relevant for this episode and we wanted to call this something super catchy and also nerdy, and definitely something that would embarrass our children.
Molly Sherwood:
Yes, absolutely.
Bethany Weathersby:
This is a little game we're calling Titer, I Just Met Her.
Molly Sherwood:
Oh, my God. Zing. Brilliant. Okay. Love it. All right.
Bethany Weathersby:
I'm both enthralled by that title and slightly offended.
Molly Sherwood:
Yeah, I'm like, what? How do we titer someone in that way? I don't know what that means. We'll just leave that to imagination.
Bethany Weathersby:
All right. All right.
Molly Sherwood:
Okay. These questions are going to be new to the other person. The topics of these are things that would specifically be relevant to the OB's role in the patient management. It's like presenting a scenario of a patient, and then the other person's going to answer what they would do in this scenario.
Bethany Weathersby:
Okay.
Molly Sherwood:
Okay. If it goes well, maybe we'll do this again throughout the season. If it's a flop, then sorry to everyone who has to suffer through this, so we'll see.
Bethany Weathersby:
Okay, that's going to be great.
Molly Sherwood:
I want to start by asking the HDFN Queen a question.
Bethany Weathersby:
All right. Let's do it. I know. I had to pause.
Molly Sherwood:
You're like, I know [inaudible] obviously. You're like, "Go on. Obviously, you're talking about me." Okay. All right. Here's my question. A mom has a bleed in her second trimester, and then she gets RhoGAM because she has a negative blood type, so she gets RhoGAM since she bled. And then, at her 28-week visit, her doctor did another routine antibody screen and she had a positive anti-D titer of eight. What do you think should happen?
Bethany Weathersby:
Okay. Do you know what week she received the RhoGAM?
Molly Sherwood:
Oh, great question.
Bethany Weathersby:
Because I know there can be a little bit of ... Remember the remaining, it can cause a positive antibody screen with a low titer for just a temporary.
Molly Sherwood:
Well, what do you think the threshold is like if she had received RhoGAM?
Bethany Weathersby:
Yeah. Well you did say second trimester, correct?
Molly Sherwood:
Yeah.
Bethany Weathersby:
Especially with a titer of eight, I would just play it safe, assume that she is sensitized and get a referral into an MFM right away.
Molly Sherwood:
And then, they can just monitor and figure out, because it could have been a false trigger from getting RhoGAM, but it also could be the real deal.
Bethany Weathersby:
But I think that that false trigger can only cause a titer of something. Do you know what that titer is? And I feel like it's lower than eight.
Molly Sherwood:
Yeah, I don't know. Because I feel like that eight is right at that threshold.
Bethany Weathersby:
Okay, okay. But see, if you don't know, just play it safe and get it to an MFM and let them decide.
Molly Sherwood:
Yep. We have a plan. All right, your turn.
Bethany Weathersby:
Okay, my turn. All right. A mother is 11 weeks pregnant with her second child. She had no issues in the first pregnancy at all. She tested positive for anti-Kell antibodies at eight weeks and the titer was 512. Her husband's blood was tested, but he came back negative for Kell antibodies. Her OB is saying there's no need to refer to an MFM now since the husband is negative for Kell. And so then, that would make the baby negative for Kell as well, right? So what needs to happen?
Molly Sherwood:
Okay. All right. This is a good one. All right. I'm listening and I was like, oh, we're good. The baby's totally good to go because the father is negative. But did you say he's negative? All right, so she has Kell and she has a really high titer, 512. That's bad.
Bethany Weathersby:
Right.
Molly Sherwood:
But you said he's negative for Kell. Did you say he's negative for Kell antibodies or Kell antigen?
Bethany Weathersby:
Antibodies.
Molly Sherwood:
Okay. All right. This is the problem.
Bethany Weathersby:
Mm-hmm. What's the problem?
Molly Sherwood:
This is the problem. The problem is he was tested for antibodies. He's not going to have antibodies. If he did, it wouldn't matter. We need to know his antigen status. We actually still don't know if the baby is at risk. So they still need an ASAP referral right away to MFM because that's a high titer for Kell. And then, get the cell-free fetal DNA testing going now.
Bethany Weathersby:
Should they order another blood test for the dad?
Molly Sherwood:
Oh yeah. Yeah, you're right. So redo that blood test. That's true because you might not need cell-free fetal DNA. Do the antigen phenotype test on the dad and then if he's heterozygous, then we go with cell-free fetal DNA.
Bethany Weathersby:
Right.
Molly Sherwood:
Do you agree?
Bethany Weathersby:
Yeah, yeah. As long as you at first get that MFM referral in, I think, just because of the titer.
Molly Sherwood:
Good question.
Bethany Weathersby:
Okay, yeah.
Molly Sherwood:
That was good. All right. I have one for you.
Bethany Weathersby:
Okay.
Molly Sherwood:
A mom is pregnant with her third child and she was just told that the antibodies were found in her first trimester blood work, she has an anti-E titer of four. Her OB says since the titer is low, they'll just wait and check the titer again at 28 weeks. The mom also looking back now is realizing that her previous child was born with jaundice and needed phototherapy. What would you do next?
Bethany Weathersby:
Right. Okay. That is a low titer for E, but just seeing that her previous baby had some jaundice and needed phototherapy, it kind of makes you wonder if that baby was also affected. If she did, I wonder if she did have those antibodies in her previous pregnancy. I think, again, she just needs to be referred as soon as possible to an MFM and they need to follow it. Sorry, I'm trying to figure out, I'm trying to remember how far along she is in her pregnancy. Do we know?
Molly Sherwood:
It just says she was just told the antibodies were found in her first trimester blood work, so maybe she's 10 weeks or something.
Bethany Weathersby:
Okay. Okay. I gotcha. Sorry, I'm thinking through it. Yeah, I would get a referral into the MFM and I would have the father of the baby tested for the E-antigen. Honestly, I would want to look back at the previous baby's medical records.
Molly Sherwood:
Yes, to see if they were positive at birth.
Bethany Weathersby:
Yes, yep. I don't know. I feel like I'm missing something. This is hard. This makes me really empathize.
Molly Sherwood:
I know. [inaudible]. Also, I don't like the waiting until 28 weeks to check again since the fetal score.
Bethany Weathersby:
Oh, yeah, of course.
Molly Sherwood:
We don't like that.
Bethany Weathersby:
Right. That's so many weeks where it could change and become critical, and then it just doesn't make sense to wait until 28 weeks.
Molly Sherwood:
Yeah, so just every four weeks, for sure.
Bethany Weathersby:
Yeah. Good one. Good one.
Molly Sherwood:
All right. Okay, lay one on me.
Bethany Weathersby:
Okay. Here we go. All right. There's a mother that she's 18 weeks pregnant with her third child. She hemorrhaged in her last delivery and needed a blood transfusion. Her OB just told her that her first trimester antibody screen came back positive for anti-Kell antibodies. And the OB has ordered blood work for her husband to see if he has the Kell antigen. The OB is saying that if the husband is Kell antigen positive, then they will refer her to a maternal fetal medicine specialist.
Molly Sherwood:
Okay. I like that they went ahead and ordered the correct blood work on the husband. That's one really good step. One thing to keep in mind is that since she's hemorrhaged and had a blood transfusion before, it might be the case that she became sensitized from the blood transfusion. So the husband really might be Kell negative.
Bethany Weathersby:
Right, right.
Molly Sherwood:
Especially because only 9% of the US population is Kell positive.
Bethany Weathersby:
Exactly.
Molly Sherwood:
But we don't know that yet. We don't know. Also, you didn't mention the titer. Do we know the titer or no? I guess not.
Bethany Weathersby:
Let's say it's 16.
Molly Sherwood:
Okay, because I was going to say if we don't know the titer, that's also a problem. We need to know that to figure out how pressing this is.
Bethany Weathersby:
Especially if she's 18 weeks pregnant, right?
Molly Sherwood:
Yeah. If it's 16 and she's 18 weeks pregnant, she should be having her MCA scans.
Bethany Weathersby:
Let's say we don't know, what would we do then?
Molly Sherwood:
Okay. If we don't even know the titer, then I think she needs to go back to her OB and be like, "Hey, did you get a titer on that when my antibodies came back positive?" So, figure that out right away. Then, the OB is saying, "If the baby is Kell positive, we'll refer," there's not really time for that. I feel like just get the referral in now and start the monitoring you need to do while you're waiting to figure out if the baby is going to be affected. There's no harm in that at all.
Bethany Weathersby:
Yeah, definitely. Even if they don't have the titer, they should first get her into the MFM because she's 18 weeks with Kell, and then try to set up an MCA Doppler while they wait for her titer results to come in.
Molly Sherwood:
Yep, I like it.
Bethany Weathersby:
Okay. All right. Hit me.
Molly Sherwood:
Okay. This is a mom who's 14 weeks pregnant, so 14 weeks and she gets a call from her OB that her first trimester blood work came back positive for Kell antibodies and the titer is 1024. Her doctor says they're going to refer her to the MFM and she's going to be seen at 18 weeks pregnant.
Bethany Weathersby:
Yep. Okay. She should call the OB and say, "I need immediate referral to an MFM because my titer is so high, the situation could be very urgent. I need to get a plan going with my MFM as soon as possible." Once that referral is in, then you can start looking at the dad's antigen status and all of those good things.
Molly Sherwood:
Mm-hmm. Yep.
Bethany Weathersby:
Yeah. Okay.
Molly Sherwood:
Agreed.
Bethany Weathersby:
A mother just found out a couple of weeks ago that she's pregnant with her third child. She has anti-D antibodies and they were diagnosed in her previous pregnancy. Her husband has never been tested for anything. Her titer is two. Her last baby did need a few days of phototherapy and in that last pregnancy, her titer did reach 16 at one point. What do you think?
Molly Sherwood:
Okay. Probably that baby was affected. We can't be sure, but looking back at that baby's medical records would be helpful. But if the baby needed some phototherapy, that might be HDFN. The husband should have been tested the previous pregnancy to figure out his antigen status and whether the baby is at risk. But anyway, in any case, now's the time to do it now. And the fact that the titer is two now, but it was 16 before, so it was once critical and we have a maybe affected previous pregnancy, that to me triggers starting MCA scans anyway. Even though the titer is now two, MCA scans should still start at probably 16 to 18 weeks. While at the same time, they're figuring out the husband's antigen status.
Bethany Weathersby:
Right. Yeah, I think that sounds great. Also in this case, this would not be someone to maybe let the OB manage it.
Molly Sherwood:
Right, right.
Bethany Weathersby:
If her titer are super low, yeah.
Molly Sherwood:
Yeah.
Bethany Weathersby:
Okay. That was great.
Molly Sherwood:
Cool.
Bethany Weathersby:
All right. We did it.
Molly Sherwood:
I like that game.
Bethany Weathersby:
I do, too.
Molly Sherwood:
All right.
Bethany Weathersby:
It's harder than I thought.
Molly Sherwood:
I know. Yeah, it was fun. But now I understood.
Bethany Weathersby:
All right, I think we did a good job.
Molly Sherwood:
All right. I think we did, too. Let's sign off. Let's wrap it up on the high note of our lovely game.
Bethany Weathersby:
I know. I have to get to the dentist, yep.
Molly Sherwood:
Oh, shoot. Very important. Okay. Very important.
Bethany Weathersby:
Yeah.
Molly Sherwood:
All right. What should we say? What do we say? Our normal thing? Should I say it today?
Bethany Weathersby:
Sure.
Molly Sherwood:
Okay, I'm going to go for it. Whether you are a patient, provider or otherwise affected by antibodies in pregnancy, we are here for you. We have great resources on our website at allohopefoundation.org. That's allo, spelled A L L O, hopefoundation.org.
Bethany Weathersby:
Thanks for listening. The Allo Podcast is a production of the Allo Hope Foundation. It was researched and written by Molly Sherwood and me, Bethany Weathersby. It's produced and edited by CJ Housh and Eric Hurst of Media Club. The Allo Podcast is sponsored by Janssen Pharmaceutical Companies of Johnson and Johnson. It's getting weird right now. So, okay. Now I'm nervous. Oh, God. Stop. Only bring me solutions. You're fired, Molly.