Sickle Cell Disease: Diagnoses, Screening, and Treatment - Episode 4

Early Interventions for the Treatment of Sickle Cell Disease

January 20, 2020

Peter Salgo, MD: Let’s take a look at some of these interventions because 1 of the oldest when I was in medical school, so we’re going way back, I think the guy sitting next to me was the triceratops in medical school, is hydroxyurea.

Biree Andemariam, MD: I think we have to go earlier than that.

Peter Salgo, MD: Really?

Biree Andemariam, MD: I thought you were going to talk about prophylactic penicillin.

Peter Salgo, MD: All right, do you want to do that? Please.

Biree Andemariam, MD: I think, if we want to start…. Well, I think Elliott could probably speak best to that.

Peter Salgo, MD: Are you saying Elliott is just that old?

Biree Andemariam, MD: Yes.

Elliot Vichinsky, MD: Yes, I am that old, and we can go back even further. But basically, the way things were, in my opinion, up until the 1960s, though the disease was studied molecularly, there was no real intervention for patients. And as communities organized and started learning more about the disease and how to do things, they understood some basic principles, early diagnosis would make a difference. And it led to the states starting to screen in newborns, and that was really important because about a third of the deaths that were occurring in infancy were occurring at the time of diagnosis. No one knew. The parents did not know the child had a disease, and at their first presentation they died, and this was because of their lack of ability to fight off an infection. So just identifying them early and educating the family to come in for fever made a dramatic difference in survival.

After that, the demonstration of giving children prophylactic antibiotics every day was done, and it had a huge effect with newborn screening in lowering the mortality rates. And as those things were developing, which really had a big difference, also education of the families about how to feel the spleen, how to monitor them for blood and other things like that. And probably the thing that’s made the most difference, in my opinion, though these therapies are critical, is in getting access to multidisciplinary care that can treat complications early.

Peter Salgo, MD: Right, and we’re going to get to that. Now, let me go on to hydroxyurea. Humor me on this one because that’s where I come in to the medical business. That’s what’s of interest to me. I get to do that. What is the role? How does it work? Does it work? Are we still using it? All these are important questions.

Biree Andemariam, MD: Yes, yes, yes, I think.

Peter Salgo, MD: Yes, yes, yes, and yes.

Biree Andemariam, MD: Yes, yes, yes, and yes.

Peter Salgo, MD: Explain yourself.

Biree Andemariam, MD: Yes, we do use it, we should use it, and we should keep using it. I think we probably all agree with that. You’re probably alluding to hydroxyurea being the first FDA-approved drug for sickle cell disease.

Peter Salgo, MD: Yes.

Biree Andemariam, MD: Was designated as such in 1998 after a landmark trial that randomized adults with sickle cell disease to either daily hydroxyurea or placebo. And from that trial it was determined that those on daily hydroxyurea had a reduction in the frequency of painful crisis episodes on an annualized basis.

Peter Salgo, MD: The end point there, that silo was the pain silo.

Biree Andemariam, MD: Correct.

Peter Salgo, MD: For hydroxyurea. And was it effective in the other phenomenon as well as pain?

Biree Andemariam, MD: Jane?

Jane Hankins, MD, MS: We’re still learning.

Elliot Vichinsky, MD: The initial trial, the randomized trial showed decreases in pain events, hospitalizations, acute chest syndrome, and number of transfusions. What happened was the study then did not have a long-term follow-up, and after that a large amount of effort was made to see what its effects on the natural history of the disease were. It’s only recently that we’ve got enough validated information to really give us the evidence that everyone with sickle cell would benefit from being on the drug.

Sophie Lanzkron, MD, MHS: Because there are data that suggest that it improves overall survival.

Jane Hankins, MD, MS: Right.

Peter Salgo, MD: Got it. Now, what about on the other side of this, the effects on fertility, reproductive health that hydroxyurea....

Biree Andemariam, MD: Those are big issues. I’m an adult sickle cell specialist, so I’ll let the pediatrician speak to that issue. But because it is now considered appropriate to initiate a conversation about giving hydroxyurea as early as 9 months, and again I’ll leave it to the pediatric hematologist.

Peter Salgo, MD: Really?

Biree Andemariam, MD: Yes. With respect to fertility issues and hydroxyurea, the general consensus, I think I can say this pretty strongly, is to not have individuals who are of reproductive potential or considering conceiving a child, whether a man or a woman, to be on hydroxyurea and to be off of hydroxyurea for the duration of pregnancy and lactation. Now, this is a challenge because we didn’t talk about this but should have, the average survival of individuals with sickle cell disease in this country is somewhere in the 40s. But I think if you talk to a lot of us, we think that that’s an overestimate. So, you’re talking about a population of individuals who almost by definition are all of reproductive potential. And until recently, having the only FDA-approved drug for this population being a potential teratogen, for which the recommendation or general consensus is to take them off, has made it hard and challenging for a lot of us who take care of adults who want to have children.

Peter Salgo, MD: Let me stop you because that’s a number that I was unaware of. My sense of this was different, but I’m sure you’re right. The life expectancy in this country of somebody with SS disease is 40?

Biree Andemariam, MD: In the 40s.

Peter Salgo, MD: In the 40s.

Biree Andemariam, MD: In the 40s. It’s slightly different for men and women, but this is based on data published in 1994.

Peter Salgo, MD: Can we just pause? I want that to sink in for our viewers, 40s.

Jane Hankins, MD, MS: Yes.

Elliot Vichinsky, MD: I’d like to point out about that. This is important. California and other states have really looked at the median, mean survival. The original cooperative study found these data and that was when I was younger, in the 40s, and when the analysis was done and what really shows is on an overall basis, that is exactly true. But in patients who are monitored aggressively with comprehensive care, the survival in that population is around 60.

Peter Salgo, MD: That’s where we’re going to go. But that’s a shattering number to me. So many people with about half the average life span of the average American.

Biree Andemariam, MD: Right.

Peter Salgo, MD: That’s untenable. We’ve got to fix this. What’s the Siklos stuff, 100 mg in children age 2 years and older?

Sophie Lanzkron, MD, MHS: It’s hydroxyurea.

Peter Salgo, MD: It is hydroxyurea, that’s it.

Jane Hankins, MD, MS: It helps us dose children because they’re smaller, and then we have to do the dosing per kilogram. And it helps us give the appropriate dose for the child.

Transcript edited for clarity.


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