Making sense out of the RDW

red cell
Q. I don’t understand the red cell distribution width (RDW)! The formula is: RDW= (MCV standard deviation/ MCV) x 100. If the standard deviation is a fixed number, why does the RDW increase whether MCV is increased or decreased? I understand that in both iron deficiency and megaloblastic anemia it should be increased cause it shows the volume differentiation but it is mathematically obscure to me.

A. Good question! The standard deviation of the mean actually does change depending on what type of anemia the patient has.

Normally, the cells in our blood are all about the same size. So the standard deviation of the mean is fairly low. Meaning that if our MCV is 90 fL, there might be a few red cells that are 88 or 89, and a few that are 91 or 92, but basically, there’s little deviation from the mean – almost every cell is very close to 90 fL in size.

In some types of anemia, there is a huge variation in the size of the red cells. In iron-deficiency anemia, for example, each new wave of iron-depleted cells is smaller than the last (because there is less and less iron around). So the older red cells are bigger than the newer red cells. If the overall MCV in a particular case is 70 fL, there are going to be some cells (the older ones) that might be close to 80 fL, and other cells (the newest ones) that might be around 60 fL. So the deviation from the mean is large, and the RDW is high.

If you think of it in terms of test scores (a topic we all know well!), it might help. The mean score for the class might be, say 80. But it’s also useful to know if everyone scored right around 80 (meaning that the standard deviation was low), or if there were a wide range of scores from 60 to 100 (meaning that the standard deviation was high). Same thing with a blood smear: if all the red cells are roughly the same size, the standard deviation (and RDW) is low. If there is a wide range of sizes, the standard deviation (and RDW) is high.

By the way, the place that the RDW is most useful (in my humble opinion) is in differentiating between iron-deficiency anemia (IDA) and mild to moderate thalassemia. In IDA, as we just talked about, the RDW is high. In mild-moderate thalassemia, the RDW is not elevated. The cells in mild-moderate thalassemia are all basically the same size – probably because the defect in thalassemia is static (unlike the situation in IDA, where the defect worsens over time, so the cells keep getting smaller and smaller).

Why do the INR and PTT measure different pathways?

test tubeCoagulation questions seem to come up all the time! Here’s a good one from one of our readers.

Q. In both the PT and PTT we add thromboplastin, right? So how come the PT measures the extrinsic pathway and the PTT measures the intrinsic pathway?

A. This is a great question because it really gets at the underlying concepts of the PT (INR) and PTT. When I was a medical student, I never really thought about why the INR only measured the extrinsic pathway and the PTT measured only the intrinsic pathway. I just memorized the substance added to the test tube in each test, and the pathway the test measured. Later on, though, I realized I didn’t have a clue as to why the tests measured the pathways they did.

Before we get into the reasoning behind the tests, a quick correction is in order. We don’t add thromboplastin in both the INR and PTT. In the INR, you add thromboplastin, and in the PTT you add phospholipids (not thromboplastin). It turns out thromboplastin is a substance that contains both phospholipids AND a tissue-factor-like substance. That’s why they call the assay the “partial thromboplastin time” – because you only need to add part of the thromboplastin reagent (the phospholipid part) to get this test to run.

To understand why the PT measures just the extrinsic pathway and the PTT measures just the intrinsic pathway, you need to know what activates these pathways in the body. The extrinsic pathway is activated by tissue factor. The intrinsic pathway can be activated by a bunch of things, the most important of which is thrombin.

Why the INR measures the extrinsic pathway
To get blood in a test tube to form fibrin along the extrinsic pathway, you need to add some tissue-factor-like substance. Also, since you removed the platelets and calcium before running the test, you need to add those things back into the test tube (the coagulation system needs a phospholipid surface, normally provided by platelets, and calcium to run). Thromboplastin is a substance that contains both phospholipids and a tissue-factor-like substance. Add thromboplastin and some calcium, and the blood in the test tube will form fibrin via the extrinsic pathway.

Why the PTT measures intrinsic pathway
To get blood in a test tube to form fibrin along the intrinsic pathway, you don’t need to add any tissue-factor-like substance (if you do, the extrinsic pathway will be activated!). All you need to do is add back what you took out of the blood (phospholipids and calcium), as well as something like silica or kaolin to activate the intrinsic pathway (normally, thrombin does this job in vivo), and you’ll form fibrin along the intrinsic pathway. This is actually why the intrinsic pathway was named the way it was: everything you need to get the pathway to run is “intrinsic” to the blood. The extrinsic pathway requires something “extrinsic” to the blood (tissue factor) for it to run.

Bottom line
The INR activates the extrinsic pathway because in this test you add thromboplastin (which contains both a tissue-factor-like substance and phospholipids) to the test tube. The PTT activates the intrinsic pathway because in this test you add just phospholipids to the test tube – and without tissue factor around, fibrin is formed along the intrinsic pathway.