Before you can really appreciate pathologic changes in red cells, you need to know what normal red cells look like.  Here is a normal blood smear image, taken at high power. There are several things to notice here.

First, the cells are nicely spread across the field. They are sometimes touching or even slightly overlapping, but they’re not all piled up on top of each other. There are occasional small empty spaces, but there are not vast barren areas the size of several red cells. By the way, you need to be in the right area of the blood smear to make these assessments. The right area – the “zone of morphology” – is a few fields in from the feather edge of the blood smear (the edge opposite the thick end of the smear). In this zone, in a normal blood smear, the cells are just barely touching, as seen in this photo.

Second, the cells appear to have a normal amount of hemoglobin. See the white dot in the center of each red cell? That’s the “zone of central pallor.” It should be approximately 1/3 the diameter of the entire red cell (cells like this are called normochromic). If it’s much larger, that means that the cell does not have enough hemoglobin (cells like this are called hypochromic) and the patient is anemic.

Next, check out the shape of these cells: they’re all round! That’s what you’d expect. Rarely, you may see a cell that looks a bit beat up, or that deviates slightly from a perfect round appearance. But overall, there are not a significant number of funny-shaped red cells (like pointy ones, teardrop-shaped ones, or sickle-shaped ones). This shape quality is termed poikilocytosis. Normal blood has minimal poikilocytosis (most all of the cells are nice and round). Some anemias, like severe thalassemia, can have marked poikilocytosis (the cells are all kinds of different shapes).

One property that is very important, but hard to gauge visually, is red cell size. It’s pretty hard to tell, just looking, whether the cells are normal in size (normocytic), small (microcytic), or large (macrocytic). You need to look at the MCV (mean cell volume), a value reported in the complete blood count (CBC), to determine whether the cells are normal in size or not. The normal MCV is between 80 and 100 femtoliters; red cells with an MCV less than 80 are considered microcytic, and red cells with an MCV over 100 are considered macrocytic. This is an important property to assess when you’re dealing with a case of anemia, because it helps you narrow down your possible diagnoses (some anemias are microcytic, some are macrocytic, and some are normocytic).

It is possible to tell, however, how much the cells vary in size. You can see, with your naked eye, whether the cells are all pretty much the same size, or whether there is a big size range from tiny ones to big huge honkers. Normal blood has minimal anisocytosis (all the cells are pretty much the same size), whereas some anemias, like severe iron deficiency anemia, can have marked anisocytosis (there are some tiny ones and some big ones). The CBC value that reflects this variation in cell size is the RDW, or red cell distribution width. If the RDW is low, that means there is minimal anisocytosis, and all the cells are pretty much the same size. If the RDW is very high, that means there is marked anisocytosis, and the cells vary in size from small to large. This is another value that can help you out when you’re trying to diagnose an anemia.

Finally, there’s nothing weird going on. There are no nucleated red blood cells, infectious organisms (like malarial organisms) within the red cells, Pappenheimer bodies (iron aggregates), Howell-Jolly bodies (little fragments of DNA that didn’t quite make it when the nucleus was extruded), or anything else funny-looking.

It’s a good idea to go through a checklist like this when you’re looking at each part of a blood smear – red cells, white cells, and platelets. Your eye has a tendency to jump to the nearest weird-looking thing, and in doing so, you may miss subtle but important changes unless you have a nice plan for how to approach a blood smear.