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).

How come the extrinsic and intrinsic pathways are named that way?

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Q. How did the “extrinsic” and “intrinsic” coagulation pathways get their names? It seems counter-intuitive.

A. Excellent question!! And one that a lot of students have asked in class. “Intrinsic” sounds like the important pathway that happens in the body, and “extrinsic” sounds like one that might happen in the lab, or outside the body. But that’s not at all what the names mean!

The two pathways were named that way because of the way blood clots in a test tube in the lab – not because of the way the pathways act in the body. Both pathways are totally necessary for coagulation to proceed in the body – let’s get that straight right off. But in the lab, you can do each pathway separately (the INR, or the PT, measures the extrinsic pathway, and the PTT measures the intrinsic pathway).

Extrinsic pathway

If you want to get the extrinsic pathway to run in a test tube, you have to add something extrinsic to the blood. Remember: the extrinsic pathway is kicked off by tissue factor combining with VIIa. Tissue factor is not normally present in the blood (it’s in little closed-up particles, or it’s in the subendothelium, or it’s in inflammatory cells…it’s a mysterious little substance). So if you want to get blood to clot in a test tube via the extrinsic pathway, you have to add tissue factor (which is extrinsic to the blood) to the test tube.

Intrinsic pathway

If you want to get the intrinsic pathway to run, you don’t have to add anything – everything that it needs is already in the blood. Remember: the intrinsic pathway is kicked off in the body by thrombin (and, less importantly, by other stuff, like bradykinin and high molecular weight kininogen). So everything you need for that pathway is already in the test tube; all the factors are intrinsic to the blood.

Of course, for both pathways, you have to replace the calcium and phospholipid surfaces you took out of the blood, because the coagulation factors need calcium and a phospholipid surface to work. For coagulation tests, you draw blood into a blue-topped test tube which contains a chelating substance that takes out the calcium in the blood (otherwise the blood would clot before you even got back to the lab). You also remove the platelets before running the tests (platelets provide a phospholipid surface for the coagulation factors to sit on in the body). But calcium and a phospholipid surface are normally present in the blood – so by adding them to your test tube, you’re not really adding anything new – you’re just replacing what you took out.

Ah, coagulation. Always a challenge! If you want to read a nice summary of coagulation (if I do say so myself), check out Clot or Bleed: A Painless Guide for People Who Hate Coag. It goes through both the intrinsic and extrinsic pathways, describes how they actually fit together in the body (which, strangely, is something nobody seems to talk about), and gives you a creative (if weird) way to remember which is which.