Wednesday, 24 September 2008

How do you differentiate between iron-deficiency anaemia and anaemia of chronic inflammation?

Although there are several clever clinical clues (how's that for alliteration?), let's concentrate on the more usual biochemical methods. We'll assume that we are looking at a microcytic anaemia, and that the only two options that we are considering are the two in this question's heading. These are the two most common causes of a microcytic anaemia, but they aren't the only ones.

The test we should now order are 'iron studies', which usually report on four parameters: serum iron concentration, total iron-binding capacity, transferrin saturation, and serum ferritin. At least three of these are potentially misleading, so let's take them in turn.

Exposed on its own, iron is a dangerous thing - it has the potential to rapidly generate free radicals, for instance. The body sidesteps this challenge by ensuring that any free iron is mopped up by a carrier protein. In the blood stream, this carrier protein is called transferrin, appropriately enough. The serum iron value thus represents the circulating iron, bound to transferrin.

The 'total iron-binding capacity' (TIBC), in turn, is a measure of the circulating transferrin itself. The transferrin saturation (% sat) is a measure of how full the potential transferrin receptors are of iron. The normal % sat is 25-50%.

Once a cell has taken up the iron that transferrin brought it, any excess iron binds to a separate protein within the cell. Usually this is ferritin, but it may be haemosiderin too. Although ferritin is thus primarily an intracellular protein, some of it is inevitably present in the blood stream, and this serum ferritin can be used as a rough measure of iron stores. The principle caveat in this regard is that ferritin is an 'acute phase protein', and is non-specifically released in countless inflammatory or infectious states. Thus even if stores of iron are low, the serum ferritin may show up as being raised.

So how do these four variables vary in iron-deficiency, as compared with 'chronic inflammation', anaemia?

To answer this one, you need to recall how the two processes differ. In iron deficiency anaemia, the body has run out of iron to the extent that it can't make adequate quantities of haemoglobin. In anaemia of chronic inflammation (ACI), however, the body is trying to hide its iron from microbes (it assumes that any inflammation comes from infection), since microbes have great need of this metal. The body doesn't want to actually get rid of its precious iron, of course. (In our ancestral past, the average amount of blood loss per person was presumably a little higher than it is today, and with every drop of blood that flowed, iron was lost. So you can't afford to throw iron away every time you get sick!) No, what it does instead is to hide it in the body's stores, to the extent that if the inflammation (read: infection) is long enough, the red blood cell production of haemoglobin starts to suffer exactly as if we were actually in an iron deficiency state.

With this in mind, we can almost answer the question from our armchairs:
  • Serum iron is low in both conditions, of course (that's why both conditions can lead to a microcytic anaemia!).

  • TIBC is high in iron deficiency, since the body is putting out as many transferrin receptors as possible to scavenge any little bit of left-over iron. In ACI, on the other hand, the body wants as little iron as possible in circulation, and so it down-regulates the amount of transferrin it produces - TIBC is thus low.

  • % sat is low in both states, although it is usually a little less low in ACI, since the TIBC is low in this condition too.

  • Serum ferritin, like TIBC, is also helpful in differentiating the two conditions. In iron deficiency, it will obviously be low, since the iron stores are depleted. In ACI, however, iron stores are normal (this is where the iron is 'hidden'), and the reading may even be high, since the inflammation characteristic of ACI increases all acute phase proteins.

Thus, in summary, TIBC and serum ferritin are the two most helpful biochemical values in telling ACI apart from iron deficiency anaemia. In the latter condition, TIBC is high and ferritin low; the opposite obviously applies in the case of ACI.


  1. Is "anaemia of chronic inflammation" the same thing as "anaemia of chronic disease" or are they different somehow?

  2. No, they're the same thing. I much prefer the version I chose to go with (naturally enough!), since it is more accurate. Labelling it as "anaemia of chronic disease" seems a little odd when you consider that among the commonest causes of it are cancer and rheumatoid arthritis!

  3. Of course, the issue is only a terminological one, and isn't all that serious. If you are happy with lumping TB, rheumatoid arthritis and cancer under the "disease" heading then all is well with either name.

    The emphasis on "inflammation" and not "disease" has one additional advantage, though, and that's that my definition would (correctly) exclude chronic diseases (like osteoarthritis) that aren't inflammatory - and thus don't cause ACI.

  4. Serum transferrin receptor is another way to differentiate the two as it will be increased in iron deficiency but normal in anemia of chronic disease/inflammation although less sensitive and specific than the markers you've mentioned.