Sunday, February 07, 2010

Anemia with small red cells.

I prefer to classify anemias according to the size of the red blood cells and for this reason I regard the mean cell volume (MCV) as the most important of the red cell indices. An MCV of less than 80 fl indicates a microcytic anemia.

Since red cell consists of mainly hemoglobin, a microcytic anemia occurs when the body can't make enough hemoglobin. Either it can't make globin or it can't make heme. Inability to make globin is almost always a congenital condition, and collectively these are known as the thalassemias. I shall write about these on another day.

The rate-limiting step in heme production is the availability of iron.

We need to obtain iron from our diet because we are constantly losing it. Everybody loses about 0.5 mg a day, mainly from bowel cells shed in the motions, though shed skin cells are also involved. Women lose on average 0.5 mg a day from menstruation (equivalent to 80ml of blood loss a month). Therefore women need about twice as much iron every day in their diet as men. During pregnancy the average extra requirement is about another 1mg spread out over the whole 9 months, though at certain times they need as much as 6mg a day. The extra iron is required to provide for the baby's blood and muscle, the extra blood in the mother's circulation and the increased muscle in the uterus.

In the diet, iron is available in a usable form in sufficient quantities, only in meat. There is iron in vegetables but in such small quantities and so poorly absorbed that it can be discounted. This is particularly true of spinach. I will write that in capitals. SPINACH IS A VERY POOR SOURCE OF IRON. A German chemist put the decimal point in the wrong place when making the calculation.

Although dietary iron deficiency is common in developing countries, it is almost unknown in the West, except in vegetarian women. Iron deficiency is almost always caused by bleeding. I used to call it iron loss anemia rather than iron deficiency anemia.

The commonest cause of excessive iron loss is menorrhagia, but it is difficult to assess. It is not something women compare notes on. Most women think they have normal periods, but a Swedish gynecologist who investigated exactly how much women who thought their periods were normal actually lost per month, found it varied tenfold, from 50 ml to 500 ml, and the person who thought 500 ml was normal was the Swedish gynecologist herself.

The most important source of bleeding is the gastro-intestinal tract. Often overlooked is aspirin. It always causes some bleeding from the stomach. It may be as little as 0.2 ml per tablet or as much as 2 ml per tablet. Occasionally it is responsible for a torrential hemorrhage. Acetaminophen (paracetamol) does not do this, but ibuprofen does.

Peptic ulcer in stomach or duodenum is less common than it used to be because it is now recognized to be a treatable infection. From the large bowel, we are most concerned about colorectal cancer. In people over 60, iron deficiency is caused by occult bleeding from colorectal cancer in 18% of cases. Therefore if no obvious cause of bleeding is apparent, a person with iron deficiency should be investigated by both upper GI endoscopy and colonoscopy. Colonic diverticulae may cause acute bleeds but they are not the cause of chronic blood loss. Angiodysplasia, abnormal blood vessels, in the large bowel can be the source of bleeding, but in my experience this is only the case when there is an associated clotting disorder.

If no obvious source of bleeding is found there are some techniques to employ to look harder. The urine should be examined for blood and iron. Hematruria from bladder or kidney cancer is important to identify, but in some hemolytic anemias iron, rather than blood, is lost from the kidneys. Blood coagulation should be tested. Bleeding disorders such as mild hemophilia or Von Willebrand's disease may be the cause. Sometimes the bleeding is from the small bowel, which cannot be reached by either gastroscope or colonoscope. Special techniques are required for these.

Does malabsorption of iron occur? People with celiac disease malabsorb fats and other vital dietary elements. What about iron? Some people think that they also malabsorb iron, but for me the evidence favors increased loss of iron-laded bowel cells. In celiac disease they are shed 7 times more rapidly. In past-gastrectomy syndromes they may be shed five times as fast as normal and 50% of those who have had a gastrectomy become iron deficient.

There are still a large number of people who have apparent iron deficiency in whom no cause will be found. Some of them have plenty of iron in their body; it's just that they cannot use it. Collectively these are known as the anemias of chronic disorders, and I shall write about these next.


Anonymous said...

Is there a simple explanation for the occurrnce of cytopenia of just one type (low platelets or low neutrophils or even anemia with otherwise normal counts) in patients with CLL and significant marrow infiltration, or do you suspect that autoimmune issues or stem cell impairments play a role?

Terry Hamblin said...

There are lots of possibilities and I shall go through them all in this series. But each case has to be individually investigated.

Anonymous said...

Thanks for your offer to explain the first comment.

I am also interested in this subject.

My local oncologist says her own theory is that there is 'theft' from myelogenous progenitors, i.e. if you boost neutrophils, then red blood cells or platelet numbers will follow.

Since all arise from the same myeloid progenitor cell, could this be possible?

You can certainly hold off answering this question as I'm sure you will answer it in an upcoming post.

Thanks for helping to explain all of this.

(BTW, anyone can see a graphic depiction of the cells that result from a hematopoietic (blood-forming) stem cell if you search on those terms. A simplified picture is at )

Anonymous said...

Dr. Hamblin, I am writing on behalf of my mother who was your patient years ago. She has had CLL for 10 years and now after a second round of Leukeran and Prednisone (1 month) after being tested positive for a Coombs test is much worse. She has been off both medications for 2 weeks and has very high fevers all day for weeks(39ยบ and higher) big swollen lymph node under the tongue, feeling nauseous and not eating, no energy, etc. What can cause this and what can we expect? Thank you so much.

Terry Hamblin said...

Could be many things. She needs to see her doctor immediately. I would need to examine her and do some more blood tests to know what is going on.

Tricia said...

I look forward to your piece on thalassemia. My daughter-in-law has the beta trait and is postponing having a family due to concern/lack of information on the risks to the child or herself. Any light you can shed would be very welcome.

Nat said...

Could you comment on the likelihood of developing iron deficiency secondary to curcumin supplementation, enough to affect hemoglobin levels? Thanks

Terry Hamblin said...

Curcumin (the yellow spice in Tumeric) is thought to have some anti-cancer activities, but has limited bio-availability when given by mouth. A good review can be found here:

One of its activities is to act as a mild iron chelator (it grabs hold of iron molecules). Could it cause iron deficiency? there is some anecdotal evidence that large doses in people with borderline iron deficiency (mainly young Indian women who are vegans) can be pushed over the edge, but so far it isn't a clinical problem that I have encountered. I will blog about Curcumin at a later stage.