RBC Health Clinical Assessment


Dr Elna Saah leads a discussion on clinical and laboratory measures that can be utilized to determine RBC health.

Biree Andemariam, MD: We’ve learned about the biochemistry. We’ve learned about the effects on the ability of the red cell to circulate. Elna, let’s talk a little more about taking this back to the clinics. Are there any lab tests or clinical parameters that you would use to measure or assess red blood cell health? How do we take what we know—biochemically, morphologically, and rheologically—and apply it to how we assess normal red blood cell health in our patients?

Elna Saah, MD: Some of them have not made their way to standard clinical practice. However, if you start from your routine CBC [complete blood count], there are things the machines can measure: red blood cell density, mean corpuscular hemoglobin concentration. How dense is the red blood cell? We have methods to translate that, looking at the red cell deformability and the elongation index. You can put the red blood celsl in hypoxic chambers, trace them to hypoxia, and see what happens. You measure the elongation index, and you can measure the viscosity with viscosity machines. The … is 1 of them that also gives you that change in the rheology. Translating the rheological measurements from the bedside to the patient gives us an idea of how deformable red blood cells are under stressful conditions.

Biree Andemariam, MD: Let’s talk about that a little more, Nirmish and Matt. We talked about sickling, deformability, hydration, and adhesion—we haven’t talked about adhesion. Let’s talk a little more about these terms, which are somewhat new. In our thinking, when we think about individuals with sickle cell disease, some are newer than others.

Nirmish Shah, MD: I’ll kick things off, Matt, and then you can add. The first thing is that [concerning what] Elna brought up, what we don’t do very well is all these other measurements that you’re talking about—the point of sickling, adhesion, hydration, deformability. We don’t do that as a standard of care. To start, we should make sure patients understand what this all means. We absolutely have these conversations with patients about their hemoglobin levels. If it hasn’t gone up, has it gone down? What’s the size of their cells? What’s the red tick count? What’s their LDH [lactate dehydrogenase]? How much hemolysis is going on? That’s been in the context of hydroxyurea, which is widely accepted as a standard of care.

Now, we’re starting to change the conversation: if red cell health is also important, what other measurements can we do to also help a patient and help us understand how well that patient is doing or potentially can do? The efforts are there to try and understand that, but we need to translate that to patients as well. Not all red blood cells are the same in a patient. Instead of focusing on the percent S in a patient—for example, 90% or 80%—we also need to find measurements that say, “How much of your red blood cells are sickling? How many of your cells are healthier?” We’re starting to move to that. I don’t think patients have a great understanding of this. The medical community doesn’t have a great understanding of what the context of this means. I’m excited that we’re starting to learn more about it and get the data. But that’s where we’re moving. Hopefully, we get more information to leverage that data to talk to our patients.

Mathew M. Heeney, MD: I agree with Elna and Nirmish. A lot of what these new tools are showing us are things we have thought about esoterically but haven’t been able to objectively show. The hope is that these new tools provide reliable, nonvariable, and more widely available information regarding the red blood cell. In membrane disorders, we have blunt tools [to measure] the hemoglobin concentration within the cells. But we don’t have good ways of understanding how pliable they are and how radiologically favorable they are. That’s where these tools may be able to give us more insight, particularly in measuring variability between phenotypes of certain patients and also response to potential therapeutics as we move down these pathways. It’s an exciting time. But we need to show that these are validated tools and becoming widely available. How we integrate these into our clinical decision-making will be a big challenge.

Transcript edited for clarity

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