Can you answer (and explain) this multiple-choice question on anemia?

Q. I am a 4th year medical student in Sri Lanka. I have a question regarding this anemia question:

Your next patient, a 65 year old Finnish bachelor, is a self-proclaimed heavy drinker. He has the following indices:

Hgb 8 g/dL (12-16)
MCV 110 fL (80-100)
RDW 13% (12–13.5)
RBC 3.5 x 1012/L (4.5-6.0)
WBC 7.2 x 109/L (4-11)
Plt 420 x 109/L (150-450)

What is the most likely diagnosis?

A. Iron-deficiency anemia
B. Thalassemia
C. Megaloblastic anemia
D. Hereditary spherocytosis
E. Sickle cell anemia

Read no further if you want to do this question on your own! Scroll down (only after you’ve figured out the answer) to see the rest of this MS4’s question.




Keep scrolling…(I have to put it way down on the page, so you won’t accidentally see the answer before you are done!)





Okay. Here’s the rest of this person’s question:

I know you said the answer is c, but in Kumar and Clark it mentions that chronic alcoholism leads to a non-megaloblastic macrocytosis.

A. Yay! I see you found my little Anemia Quiz from a while back. I remember writing this one and making the history both a little revealing AND a little confusing. Hey, they can’t be all super easy, or you’d never have to look at the indices! And then you wouldn’t learn anything.

Let’s look at the indices first, and figure out what it is, and then we’ll get back to your question.

Here they are again:

Hgb 8 g/dL (12-16)
MCV 110 fL (80-100)
RDW 13% (12–13.5)
RBC 3.5 x 1012/L (4.5-6.0)
WBC 7.2 x 109/L (4-11)
Plt 420 x 109/L (150-450)

Right off the bat, this patient has a hemoglobin that is well below the normal range, meaning that this patient is moderately anemic.

After I see a low hemoglobin, the next thing I look at is the MCV, because the MCV can help you narrow down your list of possible diagnoses. If the MCV is decreased, it means you have a microcytic anemia, which narrows your diagnosis down to iron-deficiency anemia and thalassemia (well, three, I guess, since occasional cases of anemia of chronic disease are microcytic, but that’s pretty uncommon). If the MCV is increased, it means you have a macrocytic anemia, which narrows your diagnosis down to the two types of macrocytic anemia: megaloblastic (due to B12/folate problems) and non-megaloblastic (due to lots of stuff, including alcohol toxicity). If the MCV is normal, well, you’re kind of screwed in terms of narrowing down your list of diagnoses – because the normocytic anemias are a pretty long list.

So we have a patient with a macrocytic anemia. Now what?

It would be nice if we could determine whether the patient has a megaloblastic or non-megaloblastic macrocytic anemia. However, the rest of the indices are unhelpful in determining whether a macrocytic anemia is megaloblastic or non-megaloblastic; you need to look at a blood smear for that. In a blood smear showing non-megaloblastic anemia, the neutrophils look boring and normal. But in a smear showing megaloblastic anemia, you see very cool-looking hypersegmented neutrophils (with 6 or more nuclear lobes) like this one:


Which brings us to the history part of this question, which is what you’re asking about.

When I wrote this question, I threw in “self-proclaimed heavy drinker” as a pretty obvious clue that this patient might have alcoholism. Alcoholics may develop a non-megaloblastic macrocytic anemia due to alcohol toxicity alone. However, a much more common scenario in alcoholics (weird that Kumar and Clark don’t mention this) is the development of a megaloblastic macrocytic anemia due to folate deficiency (which is fairly common in alcoholics). Dietary B12 deficiency in alcoholics – or in anyone – is pretty rare, because the stores of B12 in the body are so big that it takes on the order of years with absolutely no B12 in order to get deficient.

I also threw in “Finnish bachelor” as a seemingly obscure clue to the fact that this patient may go back to Finland once in a while to fish (I know, hang in there, it gets better), and maybe he might have eaten raw fish that contained diphyllobothrium latum (fish tapeworm), which is a rare but possible cause of B12 deficiency.

You may think I’m crazy, and maybe you’re right…but if I had $5 for every time I’ve seen “Finnish bachelor” or “Finnish farmer” in a boards or boards-style question in which the answer was megaloblastic anemia, I’d be mildly rich. Well, no, not even…I’d probably have $200 or so. But still. I can’t believe the play that phrase gets. I mean, come ON – that’s a wild series of inferences to get to megaloblastic anemia. Good thing they always give you a blood smear (or describe “hypersegmented neutrophils”) when they want you to pick megaloblastic anemia.

So to sum up our question: this patient has a macrocytic anemia, and although he could have either megaloblastic or non-megaloblastic versions, we don’t know which one he has because there’s no blood smear. Fortunately, the only anemia in the list of answers that is macrocytic is C., megaloblastic anemia. So there you go.

By the way, you can rule out the other answers simply on the basis of the MCV. Iron-deficiency anemia and thalassemia are both microcytic, and hereditary spherocytosis and sickle cell anemia are both normocytic.

Bottom line

A macrocytic anemia (MCV>100) can be either megaloblastic or non-megaloblastic, and to prove which is which, you need a blood smear (which will show hypersegmented neutrophils in megaloblastic anemia).