Preventing and Diagnosing Iron Overload

Transcript:David P. Steensma, MD: The number of transfusions that patients received, and their baseline iron status, at the time of diagnosis, are factors that determine the risk of iron overload. In addition, there are some lifestyle things that can influence iron loading. For instance, patients who are heavy drinkers. Alcohol promotes iron absorption, alcohol can also injure the liver and the heart just by itself. Patients who consume more than a couple of drinks a day regularly are going to get in trouble more quickly with iron, and with organ complications. So, there are lots of different factors that play into it, and that’s why it’s hard to make a one size fits all assessment.

When we assess iron overload, there are different ways of doing it. You can just measure a serum ferritin, and that’s potentially subject to other influences besides iron. For instance, if someone has inflammation from rheumatoid arthritis or from an infection, their ferritin will go up just from that, nothing to do with iron. So, ferritin is not a great test, but it generally correlates with little body iron.

More and more we’re seeing MRI assessment of iron, particularly in the so-called T2*, R2* MRI of the liver. I do these assays regularly in my patients when I’m concerned about iron because it gives us a quantitative measure that is more helpful than just a serum therapy. There are a few places where they have a special device called the SQUID, Super Conducting Quantum Interference Device. And the SQUIDs are very expensive, they’re very rare. So, they really are only of limited utility. But they are the most accurate noninvasive measure of iron that we have. You could always biopsy something and measure it directly from a liver specimen, for instance. But that’s dangerous. People can bleed and get infected after a biopsy. Blood tests and imaging are really how we determine what the patient’s iron status is.

Serum ferritin is the easiest and most widely available test for measuring total body iron. And it has the advantage of being inexpensive and easy to obtain. The problem with it is that it is subject to other influences. And so the threshold of concern for serum ferritin is different in different individuals. So, a normal serum ferritin range is between about 50 ng/mL and about 250 ng/mL. Some investigators start to get concerned if the ferritin is over 1,000. In the thalassemia population, it seems clear that if it’s over 2,500, that’s a level of concern. But other investigators worry, you know, they’ll say, ‘Oh 1,000 is not a big deal, but 1,500, that really concerns me.’ And so, again, this is a problem of the assay. Iron saturation, which is also a widely available blood test, is less helpful in this setting because almost all the patients have a high iron saturation. So, it’s not a very good measure of total body iron stores.

Some of the things that we do to try to avoid this situation from developing include being parsimonious about who we transfuse. If somebody’s right at the institutional threshold for transfusion but they’re minimally symptomatic, maybe they can wait till next week to get some blood. We try to minimize the number of red cells administered.

We try to avoid people taking iron supplements. So, if they’re going to take a multivitamin, they should make sure it’s one without iron. Try to curtail the amount of alcohol. You don’t have to be a teetotaler, but not more than one or at most two drinks in a day.

The other strategy is to try to treat the underlying MDS. Because if you can use red cell growth factors like epoetin or darbepoetin to raise the hemoglobin, then the patient may not need transfusion, and sometimes that state can last for several years. So, treatment of the underlying MDS can help prevent some of these complications from iron overload.

Patients who are getting transfused may be getting transfused at multiple sites, maybe getting transfused without a careful record being kept of just how many units of blood that they’re getting. And so, sometimes the number of units sneaks up on you, and the patient’s had 20 or 30 units of blood before you know it. We’re not as compulsive about keeping track of blood transfusions as perhaps we should be.

Some patients are very good about it. I have some patients that keep careful records of what the hemoglobin trigger was for the blood transfusion, how many units they got, and what date they got it. So, there are some individuals who are good at it. And I encourage them. It’s always useful data to have. But as you know, we’re not as careful about monitoring that as we should be. Sometimes that has practical consequences.

We often have protocols that have transfusion independence as an endpoint, and in order to be eligible you have to have had X units of blood in the previous 8 weeks, or the previous 16 weeks. If nobody’s kept track of that and counted them, then you have to count them and wait a little while before you know that the patient is truly eligible. That is something that I think we should be doing a better job of.

A big problem is that our electronic medical records don’t speak to each other well enough yet. My center and many others spent colossal amounts of money to put these new electronic medical record tools in, and that’s not something that’s tracking. So, you spend a billion and a half dollars, and you still don’t get this very simple useful piece of information. Maybe in the future that’ll change.

Transcript Edited for Clarity