Q. In a person with both anaemia and reticulocytosis, which is the LEAST LIKELY cause?
A. acute blood loss
B. vitamin b12 deficiency with folate therapy
C. hereditary spherocytosis
D. iron deficiency secondary to peptic ulcer disease

Dr. Krafts I am in need of some assistance with the question above. From what I know, both a. and d. are types of IDA and therefore the lab findings should show a low reticulocyte count. c. is a type of hemolytic anemia which can result in reticulocytosis, and I can’t comment on b. Which is it, and why?

A. Great question! This question is getting at the concept of the bone marrow’s response to anemia. Normally, there is a balance between red cell destruction and creation in our bodies. Our red cells last about 3 months, and then as they die, they are replaced by new red cells. If something tips the balance in favor of destruction (like, say, a hemolytic process), or if something interferes with creation (for example, a lack of iron), then you’ll see an anemia.

If you see an anemia and an increase in reticulocytes (young red cells) in a patient, that usually means one of two things:

1. there is hemolytic anemia and the marrow is compensating by making more red cells
2. there was a deficiency (like an iron deficiency, for example), but the patient is now on replacement therapy, and the marrow now has enough building blocks to start making more red cells.

Let’s go through the answers one by one.

A. You would eventually see both an anemia and an increase in reticulocytes in acute blood loss (say, from a motor vehicle accident). Immediately after the blood loss, the hemoglobin would still be normal (and the patient wouldn’t look anemic by laboratory values). But after a while, as fluid was replaced (or pulled in from the tissues), the patient would become anemic. Within a few days, the bone marrow will start to respond by making more red cells, and you’d see a reticulocytosis. So acute blood loss is different than iron-deficiency anemia. It’s a one-time thing (hopefully!) and there is enough iron stored in the body to make the new red cells that are needed. So A is wrong.

B. In B12 deficiency, the patient will make fewer red cells, because you need B12 (and folate) to make DNA. In addition, the cells look weird because with the lagging development of the nucleus as compared to the normal development of the cytoplasm, the cells become big, and the nucleus is immature compared to the cytoplasm. (These cells are called “megaloblasts.”) It might be kind of counterintuitive, but if you give a patient with B12 deficiency enough folate, you can overcome the B12 deficiency, at least as far as making red cells goes. This is because of the close interaction between B12 and folate in the production of DNA. So: a patient with B12 deficiency will become anemic, and then if you give that patient folate, you’ll start seeing a reticulocytosis. So B is wrong.

C. In hereditary spherocytosis, you’d see both an anemia (from the inherent instability of the red cell membrane, which leads to early destruction of the red cells) and – assuming the bone marrow is capable – a reticulocytosis. So C is wrong.

D. In iron deficiency anemia, you see an anemia (duh). In fact, the longer the patient is iron deficient, the smaller (and less hemoglobinized) each new wave of red cells will be. But unless you give the patient iron, you will not see a reticulocytosis, because without iron around, the bone marrow would be incapable of ramping up red cell production. What you’d see is something like the image above: some fairly normal cells, some (newer) red cells with less hemoglobin, and no increase in reticulocytes. So this is the correct answer.