Hemoglobin Measurements

HELEN: Welcome to Talking About Blood. I’m Helen Osborne, host of this podcast series and a member of the advisory board for The Blood Project. I also produce and host my own podcast series, and that’s about health communication and it’s called Health Literacy Out Loud. Today, I’m talking with Dr. Carsten Lunby, who is an exercise physiologist and professor at the University of Southern Denmark. He also is CEO of Detalo Health, a device that measures blood volume. Carsten’s accomplishments are many, including as a speaker, a researcher, an author, a co-author of hundreds of scientific papers. Carsten’s teaching philosophy is to establish an environment where students can ask questions, make mistakes, and challenge themselves. I certainly found this to be so when we jointly planned this podcast about a topic that’s new to me, hemoglobin measurements. Carsten, welcome to Talking About Blood.

CARSTEN: Thank you, Helen.

HELEN: Hemoglobin measurements, is that the same thing as routine blood tests?

CARSTEN: No, it’s not. Not in my world at least.

HELEN: Okay. Well, we’re talking to a lot of hematologists and people entering their scientific or medical careers and the public. Start from the beginning. Tell us how you understand hemoglobin measurements.

CARSTEN: Well, the hemoglobin concentration is a standard measurement which is done routinely across the planet on a daily basis.

HELEN: And- and which one is that? Say it again. The hemo- well, you and I say hemoglobin in different ways.

CARSTEN: Yeah, yeah, yeah, yeah.

HELEN: But- but say it again. You’re talking about which part of the hemoglobin measurement?

CARSTEN: I’m talking about the hemoglobin concentration. And this is also, Helen, what you are referring to when you say hemoglobin or hemoglobin.

HELEN: Okay.

CARSTEN: This is very easy tool to measure, and it’s a crucial measurement, uh, across the planet on a daily basis. What I mean when I talk about hemoglobin mass, it’s not a concentration. It’s actually the total amount of hemoglobin molecules, and you can express it in grams if you want to, or in pounds if in the US, I guess.

HELEN: Okay.

CARSTEN: So it’s an absolute measurement, not a concentration-based assessment. And of course, this is a bit more difficult to measure, but the information that you get is just so much more important, in my opinion.

HELEN: Just for our wide-ranging audience, the concentration, that’s the one you said that’s universal, happens everywhere. Just explain in a little bit more detail what you mean by concentration, and then I’m going ask you to do the same about mass.

CARSTEN: Sure. So if you go to your local doctor today and your doctor takes a blood sample from a vein, uh, this blood can be analyzed on a blood gas analyzer. And the blood gas analyzer will measure the concentration of hemoglobin in your blood.

HELEN: Okay.

CARSTEN: And hemoglobin is super important because hemoglobin, of course, transports oxygen. It has many other important, uh, factors as well.

HELEN: So in our blood, it’s not 100% hemoglobin. It’s got other things in there.

CARSTEN: Oh, yeah.

HELEN: Okay.

CARSTEN: Otherwise, if it was, if the blood was just full of hemoglobin, it would be, uh, I don’t know, as thick as concrete.

HELEN: Oh, okay. We don’t want concrete.

CARSTEN: No, we don’t want that.

HELEN: Uh, it’s how much that is in all that liquid that they take out and put in that little vial?

CARSTEN: So the hemoglobin is part of the red blood cell, right? So, and the red blood cell is one part of- of the total blood volume that you have. The other part is plasma, which I guess we can call it liquid, or if you want it very basically, water, I guess. And the red blood cells are floating in this plasma, and together, these two make up the total blood volume. And the hemoglobin is part of the red blood cells, where it is mainly used to transport oxygen.

HELEN: Thanks. I like the way you’re explaining something real complicated at a basic level. Others might know that, but we want the same frame of reference. Now can you talk about hemoglobin mass and what that is and why that’s so vital and not always considered as much?

CARSTEN: So Helen, if you went to your doctor and you had your hemoglobin concentration measured, you do this measurement to, in most cases, to say something about how many red blood cells do you have. This is the question that they are actually wanting to address. But since this is concentration-based on how much plasma you have in your circulation, the concentration of hemoglobin can be more or less dependent entirely on changes in the plasma volume, so where the red blood cells are suspended in. So this is a problem, of course, if you think you do a measurement that is, that tells, that is supposed to tell you something about how many red blood cells you have, and indeed, it doesn’t. This is where we differentiate between the hemoglobin concentration, which is easy to measure, and hemoglobin mass. So how many hemoglobin molecules do you actually have in your circulation independent of plasma volume?

HELEN: Oh, okay. Independent of plasma.

CARSTEN: Assume if you were on, uh, some diuretic medication where you lose plasma volume. In such event, your hemoglobin concentration would be high, suggesting that you have a lot of red blood cells, but indeed you just have little plasma in which your red blood cells are concentrated in.

HELEN: I had the pleasure of seeing you adjust your hands, looking at the proportions of it. Our listeners don’t do that. But I like the way that you explain that about mass. Few questions there. Why is this important and why isn’t studied enough?

CARSTEN: I will tell you in cases where this is super important. It’s super important, for example, if you have kidney failure. The kidney, they regulate red cell volume and plasma volume. And if your kidney are not working as they should, they may affect either the production of red blood cells or the regulation of plasma volume. Most kidney failure patients, they are anemic, which is based on a hemoglobin concentration assessment.

HELEN: Oh, okay.

CARSTEN: If the concentration of hemoglobin is below a certain threshold, the patients are deemed anemic. And the word anemia actually means a lack of red blood cells, not just a low hemoglobin concentration, and they’re treated for this. Chronic kidney disease patients are treated for anemia, and they should be, but they’re typically treated for a suspected loss of red blood cells or a lack of red blood cells, but indeed, as it turns out, most anemic patients do not lack red blood cells. They simply speaking, have too much plasma volume compared to a reference population.

HELEN: Oh, okay.

CARSTEN: So that there are in fact… They in fact do not lack red blood cells. They are pseudo-anemic. They are dilutional anemic. And then of course, in my opinion, such patients should not be treated against a lack of red blood cells because they have the normal volume of red blood cells, but actually just an overshoot of plasma volume, so that should be reduced instead. This is why it’s so crucial to me that we measure red blood cell volume or plasma volume and actually establish the reason for the pathology leading to a change in hemoglobin concentration.

HELEN: I get it. Thank you. You, you’re great at, like, moving me and many people along in this. Is this routinely measured? Do a lot of people know this? You’re talking about patients who are on dialysis. That’s a large population. I imagine this situation applies elsewhere too. Is this test routinely done? How is that test done? How do you find out about hemoglobin mass?

CARSTEN: So the measurement of hemoglobin mass is actually super, super simple. The measurement principle was discovered in the year and published in the year 1900 by John Haldane. You know, Helen, most of your listeners will know John Haldane because of the Haldane effect on hemoglobin. So people will, “Ah, John Haldane.” They realize who this is. But besides establishing the Haldane effect, he also established this very nice method to measure hemoglobin mass in humans. It was previously done in animals, but he did it in humans, where the basic principle is that the patient inhales a very, very small amount of carbon monoxide.

HELEN: Hmm. Ooh, that sounds scary. Yeah.

CARSTEN: Yeah. Yeah. I, I know, I hear this all this time, that this sounds scary. But you should remember, Helen, it’s the dose that kills and not the necessarily the, the drug itself.

HELEN: Oh, okay.

CARSTEN: So by… When you do these measurements with carbon monoxide inhalation, the amount of carbon monoxide that you get is only very, very little. It more or less corresponds to that what you get if you smoke one cigarette. I’m not saying you should smoke, of course, and-

HELEN: Oh, okay.

CARSTEN:… smoking is not, uh, very good for you at all. But smoking one cigarette and certainly not the carbon monoxide part of the cigarette will kill you in any way.

HELEN: So to have this test, a person has to breathe in something.

CARSTEN: Yep.

HELEN: And then they, they take the blood at that point?

CARSTEN: Almost, Helen. You inhale this carbon monoxide gas, which is supplied together with 100% oxygen, so it’s absolutely no problem to inhale this. You inhale this for a few minutes because you need this gas to distribute itself evenly in the entire circulation. If it does not distribute, then the principle, the dilution principle does not work. This is why the test typically takes somewhere between four and six minutes. After you have inhaled this gas mixture, after these four to six minutes, you take one blood sample, and in that blood sample, you measure what is the content of carbon monoxide, and this can be measured very precisely on these very same blood gas analyzer that also measures hemoglobin concentration. Based on the knowledge of then how much carbon monoxide you have added to the circulation and how much the content of carbon monoxide increases in blood, you can calculate by means of the dilution principle how much hemoglobin there must be in the circulation. It’s a beautiful physiological law, and I really love it.

HELEN: Okay. Well, is this done? I’ve certainly never had that kind of a test, but I don’t have any special, you know, things going wrong with me, I don’t think, that someone would need to know. For our listeners who are dealing with people who are sick, who are, you know, a lot of diagnostic questions out there, treatment questions, is this test widely available?

CARSTEN: No, it’s not widely available. Although the method was developed in the year 1900, so 125 years ago, it really didn’t catch on in the clinical work because until the 1980s, 1990s, it was super difficult to measure carbon monoxide in blood. But since the availability of modern blood gas analyzers, where this is absolutely no problem and done routinely on a daily basis across the world-

… the method has been revived. Is that how you say it in, in English? Sorry.

HELEN: Yes. Revived, yes.

CARSTEN: It has, I would say, it has received a revival in the 1980s, 1990s, and it has been used extensively by researchers especially. And as you mentioned in the beginning, we have now developed a medical device.

HELEN: That’s the company that you’re working with.

CARSTEN: So yes, you can do this in, in hospital settings. But since we are only a very small startup company and we just started, this can by no means be seen as a routine assessment in clinical work today. But of course, we hope that this will increase over time.

HELEN: Well, I’m interested then for our listeners worldwide, what can they be doing in their practice to do this test? You’re saying that the results, what you measure is so important to know. So I want to find out how they can do it in their own setting, and I also want to hear about the implications for treatment. You talked about anemia, but are there other situations like that? Complete this part about the test.

CARSTEN: Yeah.

HELEN: How would a clinician find this out?

CARSTEN: How would a clinician find this out? This is a very good question, Helen. They would need to buy a medical device from our company in order to do this. This is, today, unfortunately, the only means by which this can be done. So that is the short answer to that. Or they could probably go to a physiology lab where some professor has set this up and in a more manual manner, but this is not applicable to clinical work, I would say. So I would envision this to take years of work from our side to make people aware that this is actually something that you can measure today.

HELEN: Okay. Well, thank you. Keep going, doing your work. Sounds important. What, in the real world, in the everyday world, in the everyday practice, what would you want clinicians to know and do in absence of your device?

CARSTEN: If you don’t have the device, I must say, I’m biased, of course, but I would say you are out of luck, basically.

HELEN: Oh, dear.

CARSTEN: Because, Helen, I mean, if you are diagnosed, let’s assume you, you contracted kidney failure.

HELEN: Mm-hmm.

CARSTEN: And you were diagnosed anemic. There is no way you can determine whether you lack red blood cells or you have too much plasma or a combination of both without actually measuring these. This is really what facilitated me to start the process of getting this approved as a medical device, because when we first did the first measurements of anemic CKD patients some 10 years ago, this was a real eye-opener to me that patients are simply being, in my opinion, being mistreated across the planet.

HELEN: All right. I hear your passion. And your, and your, you know, your work and your efforts to make this better. But it’s not here now. People are treating patients every single day. What can they do right now? If they don’t have that information when it comes to a treatment decision for, let’s say, anemia for patients with chronic kidney disease, kidney failure, what would you recommend that they do? Or is just being aware of this enough?

CARSTEN: When you have anemia, then you would perhaps intuitively think that it would make sense to restore your hemoglobin concentrations to what normal people have. This is, this would be, be the normal thinking in my mind.

HELEN: Mm-hmm.

CARSTEN: But if you normalize hemoglobin concentrations in a CKD patient to those of a reference or healthy individuals, the mortality rate is actually enhanced. So you correct the anemia, but people die more frequently. And this is, of course, not good. At the moment, it’s unknown why this occurs. I’m pretty certain that if you treat a dilutional anemic patient, so a patient that actually has the red blood cells that he or she may need, but has an expanded plasma volume and hence a reduced hemoglobin concentration, this patient will already have, I’m just, uh, saying a number here, perhaps seven liters of blood versus the normal five liters.

HELEN: Mm-hmm.

CARSTEN: If you then treat this patient with the erythropoietin, as you will today, in order to facilitate the red blood cell volume, which it does, then your total blood volume will increase even more than what it already is, and which your circulation simply cannot handle. This is why the recommendations today is not to normalize hemoglobin concentration, but rather just to bump it up a bit. And I would be really careful in-… trying to normalize hemoglobin concentrations in CKD patients without the knowledge of what it is that they are actually lacking.

HELEN: This is really interesting. Of all the many podcasts I’ve done and people I’ve spoken with about issues having to do with blood, you’re at the early stages of this without a clear-cut, readily available solution. I want to know about ways that, um, anyone can be finding out more. There are, uh, I know you’re an avid writer about this. Have you written about this? Is there research about this, identifying the problem?

CARSTEN: Yes, of course. I mean, I am the CEO of a company, but I see myself more as a professor of physiology.

HELEN: Okay.

CARSTEN: This is what we do, we do research and we publish on this, and we continue working on this issue of dilutional anemia versus real or true anemia, a lack of red blood cells. We have a number of publications that are freely available on MEDLINE.

HELEN: Okay, good.

CARSTEN: So they can be found and downloaded there.

HELEN: Thank you. I’m sure people will be doing their research on that and learning more, so this is an awareness-raising conversation that we’re having. One last part I just am curious about because it, it’s a hot topic, I think. When you talk about what’s in the blood, how about blood doping in athletes? Is this the same thing?

CARSTEN: This is more or less what got me into working with blood initially. I, in my youth, I was an endurance athlete, and this is why I ended up doing a PhD in oxygen transport to the skeletal muscle. And endurance capacity is largely limited by the transport of oxygen to the skeletal muscle. So the more oxygen you can transport to the exercising muscle, the faster you will go.

HELEN: Okay.

CARSTEN: This is why blood doping really works.

HELEN: Oh.

CARSTEN: It’s a super efficient way of increasing your exercise performance because, one, you increase the capacity to transport oxygen to your exercising muscles since you now have more blood, but also, the expanded blood volume will facilitate the filling of the heart, the Frank-Starling heart mechanism. The more blood you have, the greater your cardiac output, the more blood you can direct to your exercising muscles. So blood doping is something that we have worked a lot with for the last 20 years or so. And, and you, you know what’s, uh, crazy in, in my world is that-

HELEN: What?

CARSTEN:… there is no direct test against blood doping, uh, established.

HELEN: Oh, there isn’t?

CARSTEN: Nope. There’s, uh, there are indirect tests that may suggest that you have done blood doping or performed blood doping, but there are none. There’s zero direct test to find out whether somebody has been doing blood doping or not. I mean, this is just scary to me because in my mind, it’s a very most effective way of increasing your endurance performance. We have known that this works since the first experiments actually in the 1940s on the fighter pilots and, and since the ’60s on athletes also. It’s super potent, and in my eyes, it’s virtually undetectable.

HELEN: Oh, my goodness, which just has tremendous implications. Sounds like you as an athlete would really appreciate this because it helps your performance. However, it’s a competitive disadvantage that, I mean, I certainly hear about in the Olympics, they’re trying to figure this out and whose medal they have to give back. So, fascinating. Carsten, you’re a fascinating person bringing in this. I’m glad that you’re focusing so much on measuring hemoglobin and the difference between concentration and mass and its implications. It sounds like what you’re talking about certainly has relevance for practicing physicians and hematologists. It also has implications for those entering their studies, whether in medicine or science, science like you, about areas that need more work and more research. I think that you found a problem and you’re focusing narrowly on that now and writing about it and doing your studies. It also is meaningful to me as a layperson, I would hope to listeners too, to be learning about the complexity of blood. It’s not just that little blood test that they take when we go to the doctor’s. It’s much more complicated than that. Carsten, thank you so much for being a guest on Talking About Blood. I really appreciate it. You raised lots of important interesting issues and questions. Thank you.

CARSTEN: Thank you very much for having me. It has been a pleasure.

HELEN: As we just heard from Carsten Lunby, it’s important to consider all that’s involved as you measure hemoglobin in the blood and different components of it, different tools to measure, and implications for treatment and practice. To learn more about The Blood Project and explore its many resources for professionals and trainees and patients, go to thebloodproject.com. I invite you to also listen to my other podcast series about health communication at healthliteracyoutloud.com. Please help spread the word about this podcast series and The Blood Project. Thank you for listening. Until next time, I’m Helen Osborne.