Patient Conversations Regarding RBC Health

Biree Andemariam, MD: Our patients are very comfortable hearing us talk about their hemoglobin levels, the hemolytic markers, even hemoglobin F. We’ve drilled all those concepts into them very well. But I agree with what all of you have touched on. Our patients and families will be really excited about reviewing their blood work. That includes an assessment of the red blood cell function. As a clinician, I’m excited about hopefully using that as a standard of care in the future. [Right now, we have] a static number, like hemoglobin, which for some patients isn’t all telling when it comes to whether they feel better at any particular hemoglobin level or post-transfusion? But there may be some correlations between red blood cell functions, assays, and clinical outcomes. We’re getting closer to that. Matt, do you want to add to that?

Matthew M. Heeney, MD: I’m a very visual person. I’m a pediatrician. For years, I’ve been trying to create images in the minds of children about what’s happening in their bloodstreams. I describe [the difference between] healthy and unhealthy blood cells. A blood cell needs to be very durable and viable, to squeeze a single file through the little blood vessels. Most the children I’m describing this to have a fondness for poopy jokes, so I tell them it’s like a blocked toilet: you have to make the blood vessels bigger to get the blockage through. I spend quite a bit of time talking about the red blood cell. It’s a simple bag full of hemoglobin that carries the oxygen and some enzymes to keep the bag happy, and we can’t lose any of those things.

When we think about sickle cell [disease], the hemoglobinopathy, and the polymerization process, I describe the hemoglobin as LEGOs. The longer your red blood cell has less oxygen, the more the LEGOs snap together. That changes the shape of the cell from a disk to a sickle cell. As the red blood cell moves through your blood vessels from your lungs 6 times every minute, it’s like shaking a bag full of nails. Eventually, 1 is going to poke through that damages the membrane, and the cell will be less viable, less bendable, and more likely to get stuck.

All these images are quite useful. Some of these new tests are putting an objective number to those. You have the point of sickling. When does all that polymerization sickle the cell? The elongation index describes the pliability or bendability of that cell; it becomes less pliable and more prone to vaso-occlusion. It’s an objective way of describing what we’ve had as ethereal visual imagery in our minds and in the minds of the kids.

Nirmish Shah, MD: Matt, your point about how patients can understand and digest the information is critical. Even when we get the number for the elongation index, maybe we should be saying, “What’s your LEGO number?” We need to figure out how patients can understand this, so they know what’s happening inside. That’s exactly what I would have said. I love your analogies, and I’ll probably steal some of them.

Matthew M. Heeney, MD: Sorry, pharma keeps stealing them. Residuals will be coming. I’m certain.

Biree Andemariam, MD: We’ll all will be stealing some of these descriptions that you have, Matt. Even our adult patients will like some of this imagery and understand it. Thank you for sharing that with us and with the audience.

Transcript edited for clarity