Sickle Cell Disease: Diagnoses, Screening, and Treatment - Episode 5
Peter Salgo, MD: Now, I’ve got all of you experts trapped here with me, so I can ask you the question that all of my colleagues wanted me to ask. When do we transfuse people with sickle cell disease and should we? And how do we decide who gets transfused?
Jane Hankins, MD, MS: We transfuse the person, not the number. I always teach my residents and follow that. If you have symptoms, the number is low and you have symptoms, that’s when you transfuse.
Sophie Lanzkron, MD, MHS: There’s an American Society of Hematology [ASH] “Choosing Wisely” campaign that we do not transfuse people just because they’re having a vaso-occlusive crisis and their hemoglobin has dropped some. It is really, as Jane mentioned, having symptoms.
Biree Andemariam, MD: There are some clear indications though, both in the acute and chronic setting.
Peter Salgo, MD: Well, tell me about that because I just thought I heard 1. I thought I heard lowering hematocrit and vaso-occlusive symptoms.
Biree Andemariam, MD: No, the opposite. She says not to.
Sophie Lanzkron, MD, MHS: Yes, symptoms of anemia, hypoxia.
Peter Salgo, MD: You’re telling me not to transfuse. Let me be clear. You’re telling me that just because they have symptoms and a low hematocrit, I don’t have to transfuse.
Sophie Lanzkron, MD, MHS: If they have vaso-occlusive crisis pain and a low hematocrit, it’s not an indication for transfusion.
Peter Salgo, MD: That’s what I thought I heard. And my colleagues who are not read into this would say, “But wait, their hematocrit’s low, they’re having pain, it’s vaso-occlusive with these bad red cells, give them good red cells.” What’s wrong with that logic?
Biree Andemariam, MD: It’s never been proven to shorten the duration or intensity of a vaso-occlusive episode, and all you’re doing is exposing patients to some of the complications that we all dread, which are: the formation of red blood cell alloantibodies, which can make it harder to get the next transfusion; and iron overload, which is a major problem in individuals with sickle cell disease.
Peter Salgo, MD: Let me turn this upside down. You’re telling me when not to transfuse.
Biree Andemariam, MD: Right.
Peter Salgo, MD: When do I transfuse?
Biree Andemariam, MD: I can start. I like to think of it as the acute indications and the chronic indications, so I’ll take the easier one. Chronic indications, the most clear-cut is in the setting of a high risk for stroke, so either you’re concerned about a first stroke or a second stroke. And this is borne out of the pediatric literature that showed if you screen children with a non-invasive test called a transcranial Doppler and you saw an indication on this test that the patient was at high risk, based on their velocity of blood flow, then those kids should be on long-term regular transfusions.
Peter Salgo, MD: But I thought I heard at this table that all people with sickle disease are at high risk for stroke, certainly higher than the population at large.
Biree Andemariam, MD: Yes, they are.
Sophie Lanzkron, MD, MHS: But we have a test to identify people who are at higher risk.
Peter Salgo, MD: You would really want to see an occlusive issue with the arterial supply to the brain?
Elliot Vichinsky, MD: The brain is a large organ and the blood supply can be in big vessels, and then when you look inside the brain, they can be very small capillaries and very small areas. The transcranial Doppler really looks at blood flow in major large vessels. So, 25% or close to 25% historically of sickle cell anemia people would have a full hemiplegia by age 45, historically. And when we started screening the Doppler in the neck and we picked up functional evidence of narrowing, over the last few decades that rate has dropped dramatically by identifying those who have an increased…with no symptoms and starting them on transfusions.
Now, the other blood vessels, the tiny ones in the brain, they can be occluded separately from the big ones. And in adult and pediatric trials, roughly about 50% of adults will have, in early adults in their 30s, will have evidence of silent infarction. So, the brain is not just the big vessels. There’s a lot of ongoing damage to the little vessels, and more data are being done in kids and adults to see if transfusions can prevent those little vessels from being occluded.
Peter Salgo, MD: If we come back to my confusion, if everybody with sickle disease is at risk, much higher risk than the general population of stroke, and if we can’t even identify the tiny vessel disease with ultrasound as we can with the larger vessels, why shouldn’t we, and just give me a reason, not transfuse these folks? I don’t know.
Elliot Vichinsky, MD: Well, we are screening now children and adults with MRIs [magnetic resonance imaging]. The ASH guidelines have recommended, and the pediatric studies have recommended that we now initiate routine MRI screening at specific points for these populations. So, we can start picking up the very high risk, either intervening with transfusions or at least identifying those who are at higher risk. While not everybody agrees, there are people who....
Peter Salgo, MD: That’s why I love doing this broadcast, it’s the cackling over here, the wonderful laughter over here, the rest of the panel.
Sophie Lanzkron, MD, MHS: The issue is that even if you identify something on an MRI, especially in an adult, there are no data about what to do with that information. And so, doing a screening MRI that may show something in a 30-year-old, it’s unclear that the right thing to do is put them on chronic transfusions, because there are no data.
Elliot Vichinsky, MD: Well, if you were a non-sickle cell patient and you had a test and you could predict they’re going to develop Alzheimer disease and they have some vague symptoms, would you do the test?
Sophie Lanzkron, MD, MHS: I don’t know. Would there be something for me to do to treat it?
Elliot Vichinsky, MD: There is more to therapy, there is a whole bunch of care that is beyond just transfusions.
Sophie Lanzkron, MD, MHS: I might favor screening for neurocognitive dysfunction.
Elliot Vichinsky, MD: I agree with that.
Sophie Lanzkron, MD, MHS: Right? Because then you have something, and there is an intervention that can be done to help those patients and provide those resources.
Elliot Vichinsky, MD: I agree with that. If you could get neurocognitive testing done, I would agree with your point.
Jane Hankins, MD, MS: Right. And then the other reason for not broadly offering transfusions for people who have brain lesions, for example, is that we know that those lesions progress even when you’re on transfusions. So for me, it’s a little bit difficult.
Elliot Vichinsky, MD: Less. They progress less.
Jane Hankins, MD, MS: They progress less but they still do. It’s not like I’m going to prevent 100% of new silent infarcts and strokes if I transfuse everybody. So for me, when I have those discussions with families, I have to be honest. I say, “I don’t know if I’m going to put your child on transfusions because there are silent infarcts here, and they’re not going to have them again. It may slow down.” And the family gets really conflicted because they know the adverse effects the transfusions are going to bring. And then there’s hydroxyurea. We have some evidence hydroxyurea could slow down, too.
Elliot Vichinsky, MD: That’s true.
Peter Salgo, MD: In the era, before we were able to screen for HIV, before we had an effective screening for hepatitis C, I personally could understand more of the reluctance to transfuse. The hemochromatosis bothers me obviously, and it’s a balancing act. I don’t know, I’m confused, my colleagues are confused.
Elliot Vichinsky, MD: I think the bigger question, we can get into therapeutic interventions with transfusion. But I think the overriding concept that is important to me is that it’s a neurodegenerative disease and that the kids and adults, they’ll have progressive problems over time. And as they get older, in multitasking, certain adaptive tests that most people have, they may have more difficulty with, which would limit their ability to go through a complex health system. And so at least the physicians and medical community need to understand that as they age, they may be developing more difficulty in cognitive, managing a complex bureaucracy, and that this isn’t a sign of behavior or maladjustment, it’s a sign of neurodegenerative issues. And we need to be aggressive whether with navigation skills or other techniques. But at least recognize when you deal with these people that they have a neurodegenerative disease.
Transcript edited for clarity.