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Anemia

In terms of the diagnosis of anemia, most anemias can be sorted out with just a complete blood count anemia, anemea; that’s using not only the hemoglobin and hematocrit but also things like the RDW, the MCV and the MCH. A reticulocyte count, which I think is really an important test, and if possible a peripheral blood smear. There really are two different ways to look at anemias. Both of these are complementary. One can think of anemia using a pathophysiologic approach. It is also quite acceptable to look at anemias on the basis of morphology. I’m going to go through

In terms of extrinsic causes of hemolysis, I think they can most easily be divided into immune versus non-immune. When you think about immune-mediated hemolysis keep in mind that the red cell morphology may seem fairly normal. You may see a few spherocytes. You may see a little bit of rouleau formation, which is red cells sort of clumping in ways that look like a roll of Lifesavers. But say for that, with immune-mediated hemolytic anemias, your peripheral blood smear will appear fairly normal.

Decreased production would be another reason for anemia. This can be as a result of a generalized bone marrow failure syndrome, such as Fanconi’s anemia. It can also be a pure red cell aplasia and that can occur either as a congenital abnormality - such as a Diamond-Blackfan anemia. It can also be acquired such as in transient erythrocytopenia of childhood. We’ll come

Aplastic anemia. I trust now many of you have encountered this term. It’s obviously a misnomer because typically aplastic anemia is pancytopenia. It’s not just anemia. These patients can present initially as anemia but they go on to have other cell lines involved. Again, this can be part of a congenital process, such as Fanconi’s anemia. Keeping in mind of course that these are children who

Finally, substrate deficiencies, such as an inadequate amount of either folate, B12, iron, thymine, can all cause decreased red cell production. Malabsorption, which can be seen in certain physiologic states and also in certain other disease states, can cause anemia on the basis of not having adequate substrate to produce red cells. Mechanical interference; where you actually have

It is an important differentiation and that is between TEC, transient erythrocytopenia of childhood, and Diamond-Blackfan anemia. There really are some distinct differences. TEC is actually a fairly common disease, whereas Diamond-Blackfan is something that you should expect to encounter very infrequently in your careers. Typically Diamond-Blackfan patients become anemic and therefore symptomatic within the first year of life. But by and large we don’t really consider TEC to occur in that age

Blood loss is a fairly obvious cause of anemia in children, although sometimes the actual location of the blood loss is not clear. The most common causes of acute blood loss in children would be things like epistaxis or trauma. Certainly if a child had an

So this is looking at things from a pathophysiologic approach, which basically we are going to go through the same information by using a morphologic approach. So going through the first set of morphologic anemias, the first group that I think about are the macrocytic and it’s probably because they are actually the most straightforward. Macrocytic anemias typically are just that; cells that are unusually large. They can certainly be drug-induced. The most common drug that causes macrocytic anemia are things like sulfa drugs, like Bactrim. But when you think about … assuming that we’ve ruled out a drug-induced macrocytosis, it really does require some additional analysis beyond the first things that we talked about. Beyond a CBC, retic count and blood smear,

This next slide is a peripheral blood smear of macrocytic anemia. In addition to seeing these unusually large cells, there may also be some anisocytosis or variation in size. The other thing that you would expect to see, especially with B12 deficiency, are

Normocytic normochromic anemias are probably the most complex to sort out. The differential for normocytic normochromic anemia is much longer, so it really does require spending a little bit of time going through this. Your reticulocyte count is actually going to be very important in differentiating into two large groups the causes of a normocytic normochromic anemia. Let’s start

For patients who have a normocytic normochromic anemia and have a high reticulocyte count, these are patients who we can assume that they are anemic on the basis of increased destruction. So in that sense, morphology again is important. If you have normal morphology but you have a normocytic normochromic anemia, then consider blood loss. Because certainly in any child who starts out with a normal baseline, at least in the initial post-trauma period, their anemia should be normocytic normochromic. Certainly with chronic blood loss that can change but by and large with acute blood loss there should be normal blood cell

If you see red cell fragmentation, again we’ve talked about his before, think about things like a microangiopathic process like HUS, or a Waring Blender-type syndrome because of a cardiac prosthesis. Also think about a red cell enzymopathy; with G6PD you tend to see blister cells or cells that seem to have … they look like Pac Man cells. It’s like there is a little bite that has come

Microcytic hyperchromic anemias I think are the ones that you will see most often in your practice. Again, your reticulocyte count should help you in differentiating between several of the different diagnoses. For those that are associated with a low reticulocyte count, again because of decreased production, the things to think about are iron deficiency, lead poisoning. You can also see a microcytic hyperchromic anemia with chronic infections or with severe malnutrition. Obviously things that would be

Iron deficiency anemia. I think many of you are familiar with this and have seen plenty of this. The most common cause of iron deficiency is a physiologic or requirement that there are certainly periods of time where the growth of the individual or the demands for iron simply exceed the iron stores and that can certainly occur with a growth spurt in late infancy and also during adolescence. It can occur in menstruating young women who are on inadequate diets. It can also be a normal part of pregnancy. You can have iron deficiency also on the inability to assimilate or take up iron. That can be on the basis of an iron-poor diet, which I think is probably the most common in children, or it can be because of poor iron absorption. Other things to consider, again, are blood loss - and that is when we are talking about acute blood loss would cause a normocytic normochromic anemia - but with chronic blood loss you would eventually become iron deficient. GI bleeding would be the most common cause of that, but sustained, very heavy menses can also cause it. And certainly, in our very sick neonates, I think that many of us have experienced their anemia being on the basis of frequent blood draw.

Going on to the hemoglobinopathies as causes for anemias. This is just a reminder of exactly the components that are in hemoglobin. Keep in mind that hemoglobin is made up of four globin chains as well as a heme moiety and that’s what contains the oxygen. But typically when we talk about the hemoglobins, we talk about them with respect to having two alpha chains and then a variant chain; either gamma, beta or delta as their variant chain. When we talk about the thalassemias we are going to cover Cooley’s anemia, or beta thalassemia, hemoglobin E a disorder that some of you may be familiar with but it’s actually a

Alpha thalassemia is an important entity to differentiate because there are several different states with an alpha thalassemia. When you have a … alpha thalassemia is caused by a deletion of one or more globin genes that paired on chromosome 16. If you have a single gene deletion you usually are not anemic and that’s usually the silent carrier state. A two gene deletion, or what we would call thal trait, is also called alpha thalassemia 1, is on the basis of a two gene deletion. A deletion of three alpha globin

Beta thalassemia is caused by a number of different mutations on chromosome 11. Remember, these are quantitative hemoglobinopathies so the problem is that they actually don’t make enough beta globin. They tend to have … if you have beta thalassemia, you don’t have enough beta globin chains so you have a lot of free alpha globin chains in the red cell. They attach to the membrane and tend to cause hemolysis on that basis. These are children who typically present between 6-12 months of age.

Hemoglobin E is another type of thalassemia that’s important to mention, primarily because it’s fairly common in Southeast Asian populations. When you have homozygous hemoglobin E you tend to have very few problems, if any problems. It tends to cause a mild anemia and if anything, what you tend to see is some target cells on the peripheral blood smear. What’s most important, however, is that if it is combined with beta thalassemia. So if a child acquired a beta thalassemia trait from one parent and hemoglobin E from the other parent, this syndrome called hemoglobin E beta thalassemia is the same as any other beta thalassemia. So these are children who will become transfusion-dependent and need to be identified up front, need to be managed aggressively.