Okay, we’ve talked a lot about the DAT, and how it’s used to determine whether your patient’s hemolytic anemia is due to immune causes (warm or cold autoimmune hemolytic anemia). But how do you know if your patient’s anemia is a hemolytic one in the first place?

Well, you can look at the patient. In addition to the usual signs and symptoms of anemia (pallor, fatigue, breathlessness), you may see additional signs that indicate that the anemia is hemolytic, such as jaundice (from bilirubin, a yellow-colored breakdown product of the heme molecule), or splenomegaly (some types of hemolytic anemia are accompanied by a big spleen). But these signs are non-specific; they can occur in disorders other than hemolytic anemia.

For good, definitive proof of a hemolytic process, you need to look at lab results.

First, you should see signs that the red cells are being destroyed. These include:

1. Hemoglobinemia and/or hemoglobinuria (as evidenced by pink serum and/or urine)
2. Increased unconjugated bilirubin in the serum (this occurs when red cells are being destroyed faster than the liver can process the bilirubin)
3. Increased lactate dehydrogenase (LDH is an enzyme present in a lot of cells, including red cells; when you bust open red cells, their LDH is released)
4. Decreased haptoglobin (a protein that binds free hemoglobin; if there’s a lot of free hemoglobin around, the amount of free haptoglobin – without bound hemoglobin – goes down)

You should also see signs of accelerated erythropoiesis, the most useful of which is an increased reticulocyte count. Reticulocytes are young red cells that are a little bigger and have more RNA than mature red cells. We all have a small percentage of reticulocytes in our blood, but if there is hemolysis, the number of reticulocytes should increase.

Besides looking at these lab tests, you can also look at the blood smear for clues. Most hemolytic anemias have at least a few spherocytes (the smaller, darker red cells with no central pallor in the above image), because no matter what is causing the hemolysis, cell membrane is being lost at a greater rate than the stuff inside the cell, and when that happens, the red cell “rounds up” because it has less membrane to contain the same volume.

Some hemolytic anemias also have other abnormally-shaped red cells, like sickle cells (in sickle cell anemia), schistocytes (in microangiopathic hemolytic anemias) and bite cells (in glucose 6 phosphate dehydrogenase deficiency).

You will hopefully see an increased reticulocyte count (as explained above), and you might even see some nucleated red cells (very young red cells, still containing nuclei, that the bone marrow releases accidentally in its hurry to get mature red cells out in the blood) – both of which indicate that the patient’s bone marrow is working hard to replace the destroyed red cells.