Advances in the Treatment of Sickle Cell Anemia - Episode 8
Ify Osunkwo, MD, MPH: One of the most common treatment modalities for sickle cell disease is the use of red blood cell transfusions. Matt, can you share with us how do we use transfusions in sickle cell disease? What are the indications for simple, chronic, intermittent transfusions, and what are the potential risks and benefits of using transfusions?
Matthew M. Heeney, MD: Transfusion is a very important aspect of the therapy of sickle cell disease, but it has to be used appropriately. I sort of think of it as in the acute therapy or in the chronic therapy, and we’ll discuss those a little bit individually. The patients with sickle cell generally are quite anemic, and there can be accentuated times of anemia. The patients are very reliant on their robust red blood cell production by the bone marrow to accommodate for the shortened red cell life span. There are certain times when that red cell production is attenuated, whether it’s related to viral infections, classically parvovirus, or another where the patient will need a transfusion because their anemia is lower than even their low baseline.
There are other times when acute transfusions or intermittent transfusions are used, particularly to prepare patients for surgery or to prepare patients for other clinical intervention.
The patients over time—for other reasons for acute treatment—really the big 1 probably would be acute chest syndrome. As it was alluded to by 1 of the panelists, it is the leading cause of death in both adults and children with sickle cell disease. The process of acute chest syndrome can be ended within a simple transfusion or, in some cases, the need to do an exchange transfusion to provide more normal hemoglobin A for the patient.
On the chronic transfusion side, there really is only 1 indication, and that’s for stroke prevention, whether it’s primary stroke prevention or secondary stroke prevention. We don’t tend to use chronic transfusion for the indications of pain. That would be 1. Typically, that’s not what we use; it’s often a secondary intent of a transfusion. The only clearly indicated chronic transfusion, monthly transfusion, to suppress the amount of sickle cell hemoglobin is for stroke prevention.
Transfusions are very useful but have to be used carefully. In the United States, for the most part, blood donors are of the ethnicities that are not commonly affected by sickle cell disease, and there are minor blood group antigen differences that can lead to allosensitization or the patient creating an antibody toward the donor’s minor blood group antigens. For that reason it’s very important when considering transfusing a patient to do not only the typical cross-match of ABO and Rh compatibility but also an extended cross-match if available. In many centers patients will actually have their red blood cell antigen genotypes, so they’re able to do even a much broader matching for patients.
The other complications are just like in any other patient. You can have acute transfusion reactions, whether they’re allergic or hemolytic febrile reactions, and those are also potentially problematic.
In patients who are getting recurrent transfusions, of course we worry about infections and the concerns for HIV and hepatitis B—those are very uncommon nowadays—and the time to screening. But there are new potentially blood-borne pathogens, which are important in sickle cell disease every year. It’s Eastern equine encephalitis virus, West Nile virus, Zika virus.
In New England, where we are, we worry about tick diseases in a patient who is functionally asplenic, it will definitely cause serious disease. But the biggest feared 1 for all of us up here is allosensitization, because you further limit the number of donors. That’s when a patient really needs a lifesaving transfusion, and they may not be able to get 1.
The final complication of transfusion is that with each unit of blood comes 250 mg of iron. That iron can accumulate in the body as a feces, and we don’t have a way to get rid of iron, except for a little hair loss, skin loss, and menstruation. This iron builds up in the body rather rapidly. Even in adults who’ve had intermittent transfusions, maybe 1 a year over the course of a few decades, they can become significantly iron overloaded. And in those, that iron tends to have a predilection for the liver and the endocrine organs of the pituitary, the pancreas, and the thyroid in particular, and this can lead to added morbidities. Looking at chelation, pharmaceutical chelation to remove that iron is also something that definitely needs to be kept in mind for patients who have received a significant burden of transfusion.
Ify Osunkwo, MD, MPH: It’s often important to track how often and where they get transfused and communicate across institutional lines the type of blood that this person should be receiving, right? Have you had any experiences where that didn’t happen and something went awry?
Julie Kanter, MD: You know, it’s interesting. It’s a problem because there’s no universal—just as we don’t have a registry in sickle cell disease, there’s no blood registry that’s universal. It’s important that we teach all our patients, first of all, to only get transfusions if they really need it. While it might alleviate the symptoms of a crisis, they could add additional morbidity if they get new antibodies, right? Also, make sure the blood bank knows how to transfuse them appropriately.
Ify Osunkwo, MD, MPH: And know that they have sickle cell disease.
Julie Kanter, MD: And know that they have sickle cell disease. And know that if they’re usually treated at this hospital, you should call this hospital’s blood bank. Because they could have antibodies that then don’t show up the next time.
Nirmish R. Shah, MD: I think it warrants repeating the concept that an acute pain crisis is
not treated with a blood transfusion. Going back to what you’re saying, again, ask your patients, “When did you get your last transfusion?” They can at least have this discussion with the patient themselves. So many times I’ve had patients saying, “Dr Shah, they were trying to give me a transfusion, but you gave me that talk about how I needed to be concerned.” I think it’s a misunderstanding, and I think with ongoing education by the patients and the family and also by the providers, to understand that there are strict guidelines to give the transfusions for all those reasons that Matt discussed.
Julie Kanter, MD: You know, that’s also important. I’ve had patients say, “You know, I refused the transfusion. You told me not to get it, but the doctor got mad at me.” Or the doctor said, “Well, all you want is pain medicine.” “The truth was that I knew that I could get treated for my pain without a transfusion, and you said that was really important.” Really encourage providers as well to reserve those transfusions for acute chest syndrome and to really make sure you’re matching them correctly.
Ify Osunkwo, MD, MPH: Because there may come a time when they need it, and they have 15 antibodies and nobody in this world has available blood that matches their phenotype, and they cannot get transfusions. That has actually caused death in some patients.
Biree, share with us some experience that you’ve had around communicating around transfusions—in state, out of state—where they go. I think it’s important for us to highlight how important it is that people track where they got their last transfusion, where the samples were, where they document to antibodies, and why that’s important if they go to a different location to get care.
Biree Andemariam, MD: Right. I will tell you, at our center, when we’re seeing a new patient, an important part of our history is the transfusion history, and we ask them every single hospital they think they’ve been transfused in during their lifetime. Our blood bank calls every single one of those hospitals to ask if that patient has ever shown evidence of an antibody. I think it’s that kind of investigative work that protects patients. We would like to be able to tell our patients about all their antibodies. But quite honestly, it’s very hard for them with this chronic disease and with some of the cognitive deficits there to maintain knowledge of that level of detail.
There are programs, including ours, that give patients or caregivers copies of all of their antibodies. They can keep it on a card in their wallet, so when they go to a new hospital they can say, “Look, I’ve got all these antibodies. They may not be present at this time. They’re a little tighter. Please don’t give me any blood that’s incompatible.” It’s not easy. I wish we did have a registry, as Julie said, but we don’t. We have to do it the hard way, but it’s necessary.
Ify Osunkwo, MD, MPH: It’s important to know that they’re chronically anemic. A hemoglobin of 8 g/dL in a person with sickle cell hemoglobin SS is actually their baseline, and it’s not a reason for a transfusion. If they’re not symptomatic, you want to reserve that blood for when they really need it. People have gone through a crisis, gone down to 6 g/dL and come back up to 8 g/dL without blood, and they did just fine. I think defining their indication for transfusion is important. Are they symptomatic with tachycardia, hypoxemia, fainting spells, low blood pressure, or they have acute chest syndrome? That would be when you would consider giving a transfusion, but not just for a hemoglobin number per se.
Transcript edited for clarity.