What else, apart from infections, causes a raised white cell count?

Most authorities agree that the normal range for leukocytes (white blood cells) is between about 4 and 11 x 10⁹ cells per litre.

The commonest cause of this is, as you rightly point out, infections (of various natures).

Apart from this, though, there are numerous other causes. The best way, in my opinion, to classify a leukocytosis (raised white cell count) is to think of the two main pathophysiological options. In other words, is the increase in the number of white cells an appropriate response by the bone marrow to a stimulus (e.g. an infection), or is due to inappropriate bone marrow activity (e.g. due to leukaemia)?

For those medical students who need substantially more information on the topic, I can heartily recommend this article on the topic from the American Family Physician journal. What follows is largely based upon it. If, however, you just need a rough summary/overview, read on...

Appropriately-responding bone marrow

• Infections (already covered)
• Inflammation/hypersensitivity - probably the second most common cause. Specific examples in this category include burns, autoimmune diseases (e.g. rheumatoid arthritis), tissue necrosis (e.g. muscle infarction) and severe allergic reactions. Remember, white cells don't just fight infections, they have other roles too. For instance, after extensive burns, they are required to mop up all the dead tissue, and so the patient mounts an immune response. (There are almost always bacteria to deal in addition)
• Bodily stress - e.g. seizures, overexertion. I'm not sure of the reason behind this one. Perhaps increasing leukocyte output is simply a general response to any stress, even if it is pointless in some instances?
• Drugs - this is a commonly overlooked category. Examples include corticosteroids, beta agonists and lithium.
• Splenectomy - the spleen usually houses a significant portion of the leukocyte pool, and so its removal causes a temporary increase in the white blood cell count. After a little while (weeks, usually), the body figures this out and the leukocytes return to their normal range.
• Haemolytic anaemia - the loss of red blood cells seems to signal a non-selective increase in both red and white blood cells. Again, why the non-selectivity...? Perhaps it is in a blind attempt to deal with the cause of the haemolytic anaemia, which may often been an infection. Or perhaps its to cope mopping up the debris, which again requires white blood cells. Suggestions?

Abnormal bone marrow

• Leukaemias (acute or chronic)
• Myeloproliferative disorders (e.g. polycythemia ruba vera)

Gulp! That last category is particularly nasty, isn't it. Shouldn't we fully investigate each patient with a leukocytosis, lest we miss a leukaemia?

No, we can relax a little more. The 'abnormal bone marrow' category accounts for well less than 1% of all leukocytoses. Imagine spending tens of thousands of (say) dollars every time we got a cold! Remember also that safe medicine is about knowing when not to investigate unnecessarily too.

So instead of unhinged panic based on one isolated lab reading, we should rather look at the broader picture confronting us. Most times, the cause will be obvious (e.g. an abscess), and we can always try to treat the immediate cause and see if the leukocytosis resolves. Also, there are a few warning signs/symptoms that we should be on the lookout for. If they are present, the patient warrants a more extensive workup. The list given from the American Family Physician journal's article is appropriate, I think:

• Leukocytosis > 30 x 10⁹ per litre
• Concurrent anaemia or thrombocytopenia
• Hepatomegaly, splenomegaly or generalised lymphadenopathy
• Bleeding, bruising or petechiae
• Chronic lethargy or significant weight loss
• Lift-threatening infection or immunosuppression

There is logic behind each of these criteria... but this post is long enough already. If you have any questions, leave a comment here, or send me an email.

Jeremy

EDIT (12/02/08): What is very helpful in determining the cause of the leukocytosis is to get a breakdown of the proportions of the various subtypes of white blood cells - the 'diff. count'. For instance, very high eosinophils implies a parasite infection, perhaps... There's quite a lot more to the workup of a patient with an unexplained leukocytosis (including a peripheral smear, for instance), but I want to keep this post as focused as possible.