What does megaloblastic mean?

Here are a few great questions about megaloblastic anemia I received by email.

Megaloblastic vs. macrocytic

Q. Do I have to say “megaloblastic macrocytic” anemia? Aren’t megaloblastic and macrocytic the same thing?

A. Macrocytic refers to the size of the mature red cells in the blood. It means that the red cells are big. Normal is 80-100 femtoliters. If the red cells are over 100, they’re macrocytic; if they’re under 80, they’re microcytic.

Megaloblastic refers to the weird morphologic changes (immature nucleus, mature cytoplasm, large overall size) you see in red cell precursors (and, to some extent in neutrophil precursors), in patients who are B12 deficient. So the term is really referring to the cells in the bone marrow, not mature, circulating red cells. However, you can also see changes in the blood that indicate megaloblastic anemia, the most common of which is hypersegmented neutrophils (like the one above).

So the terms are not equivalent.

That being said, you don’t need to say both terms if you have a megaloblastic anemia, because all megaloblastic anemias are also macrocytic. You just say “megaloblastic anemia.”

Conversely, if you just say “macrocytic anemia,” that doesn’t say anything about whether there are megloblastic changes present or not! It just says: there’s an anemia, and the red cells are big.

Non-megaloblastic anemia

Q. What really is non-megaloblastic anemia? Because my lectures have mentioned it but I’m not sure what it really is.

A. Non-megaloblastic anemia just means an anemia without megaloblastic changes – and technically, that encompasses every single anemia except megaloblastic anemia! But really, when people say non-megaloblastic anemia, they’re usually referring to a macrocytic anemia (one in which the red cells are large, over 100 femtoliters) without megaloblastic changes (funny looking red cells). This type of anemia can be seen in liver failure and in myelodysplasia.

Pernicious anemia and megaloblastic anemia

Q. I don’t understand the difference between pernicious anemia and megaloblastic anemia. Pernicious anemia is just a deficiency in intrinsic factor that helps with absorption of B12…so patients have low B12 levels. But how is that different from megaloblastic anemia?

A. The best way to think about these two terms is: pernicious anemia is one cause of megaloblastic anemia.

Megaloblastic anemia is a type of anemia in which you get weird morphologic changes (megaloblasts, hypersegmented neutrophils, oval macrocytes) due to a lack of B12 and/or folate. There are lots of things that can cause a lack of B12 and/or folate…so when you see a case of megaloblastic anemia, you have to investigate to find out what the cause is.

Pernicious anemia (in which patients can’t absorb B12 due to a lack of intrinsic factor) is one cause. Another cause is folate-depleting drugs (like chemotherapy drugs); another is dietary deficiency.

It’s kind of confusing because they put the term “anemia” in pernicious anemia – so it makes it sound like pernicious anemia is a category in and of itself. It’s not – it just falls under the heading of megaloblastic anemia.

 

 

 

 

 

 

Blood cookies!

Okay, that was disturbing. But it was a lot of fun making cookies in the shape of different blood cells for our lectures on anemia and leukemia this week! (more…)

Microcytosis and hypochromasia

IDA1

Q. What is the pathophysiology of microcytes in iron-deficiency anemia (IDA)? I mean I understand that hypochromasia is due to low hemoglobin content, but what makes the cells smaller? Is it something like first there is hypochromasia and then the cells shrink? Aren’t hypochromatic cells normocytic? Why don’t red cells keep shrinking as they become hypochromatic? Please help. The question is bothering me a lot. 🙂

A. First of all, you’re right: in IDA, the red cells do get smaller. Since the bulk of the red cell is composed of hemoglobin, the less hemoglobin there is in the cell, the smaller the cell volume, and the smaller the cell overall. So in iron-deficiency anemia, there is less iron around, and therefore less hemoglobin – so the cells are smaller than normal. Same thing happens in thalassemia: less hemoglobin around (though not because of iron, but because of a genetic defect in a hemoglobin chain), so the red cells are smaller.

Just to clarify: chromasia just refers to the amount of hemoglobin in the cell. Cells can be normochromic (as they are in normal blood), or hypochromic (as they are in IDA). The size of the red cell is measured separately from the chromasia. Normally-sized red cells are called normocytic, small ones are called microcytic, and large ones are called macrocytic.

You asked if hypochromic cells are normocytic – and for the reason stated above, the answer is no, they usually aren’t. They are usually microcytic, because there’s less hemoglobin in the cell, so the cell gets smaller.

Finally, to answer your last question, in iron-deficiency anemia, the red cells do keep shrinking as they become more and more hypochromic! Assuming the iron deficiency is a continuing problem, as each new wave of red cells is produced, there will be less and less iron around – and the cells will get smaller and smaller.

So when you look at a blood smear from a patient with IDA (like the one above), you’ll see some cells that are a little bigger (these are older red cells that were made when there was still a fair amount of iron around), and some that are a little smaller (these are newer red cells, made when the iron level had dropped). Check out the two cells in the center of the image: both are hypochromic, but the one in the center is about twice as big as the one to its left.

This is why you can use the RDW to help differentiate between IDA and mild-moderate thalassemia!

Intrinsic vs. extrinsic anemias

fibrinQ. Can you help me understand intrinsic vs. extrinsic anemias? My concept of it is that intrinsic means it’s in the blood vessels and extrinsic means it’s in the spleen. (more…)