Red Blood Cells: Why Are They So Important?
Most people have little reason to know about white blood cells. But everyone knows about red blood cells! Heck, blood is red because it is full of red blood cells. Next obvious question, what makes red blood cells red? Answer: because red blood cells have a molecule in them called hemoglobin (also spelled as haemoglobin if you are Brit, and abbreviated to Hb, Hgb or Hg) and hemoglobin is colored a bright cherry red when it is rich in oxygen, but more bluish red in color when it has been stripped of its oxygen. Did you know hemoglobin is present to the tune of 95-97% by dry weight of red blood cells (if water is counted, then the weight percentage of hemoglobin is around 35%). Think of red blood cells as little sacks full of water and hemoglobin and you will be right on the mark.
At the center of the hemoglobin molecule is a heme group, with an iron atom at the center of it. Nature really hit a home run with this stuff. When hemoglobin comes in contact with oxygen in your lungs, oxygen gets attached to the iron atom. After picking up this precious hitchhiker in the lungs the blood next goes to the heart – the pumping station which circulates blood throughout your body. This oxygenated version of hemoglobin is bright red – which is why arterial blood leaving the heart is bright red.
As it goes through the body, hemoglobin gives up its oxygen to the various cells it comes in contact with. Each cell in your body breathes. It needs oxygen to convert food (glucose) to energy. Without oxygen, the cell dies – rather quickly. If too many cells die, you die. Depleted oxygen supply to the cells is slow suffocation, and that is exactly what it feels like. Once the hemoglobin has given up its oxygen to the cells it picks up the waste byproduct of cellular breathing, namely carbon dioxide. Venous blood returning to the lungs and heart is bluish red in color because hemoglobin with carbon dioxide attached to it is bluish red in color.
When this wonderful oxygen transport from your lungs, through your heart to the rest of your body is messed up for some reason, you have anemia. Since anemia is a common side effect of CLL and causes significant loss of quality of life, we need to learn about it.
Tracking Red Blood Cell Counts
I used one of my own prior CBC reports to illustrate white blood cell counts in my last article. Here is the same report, now expanded to include red blood cell parameters. Let us take the new items (color coded red) in this report one at a time, explaining each of the acronyms. As I said before, the important thing is to get the general lay of the land, not necessarily get all this stuff by heart right now. There is no pop-up quiz that you have to ace. As long as you know you can find this information again when you need it, you are good to go.
Red Blood Cell Count (RBC)
As the name implies, this is the number of red blood cells in a specified amount of blood. This report says I have 4,590 red blood cells in every microliter of blood. And as you can see from the reference interval given for healthy individuals, I am doing OK on this front. Reference ranges are even more important in the case of red blood cells because they are different for men and women. Most labs give ranges appropriate for the sex of the patient.
If I were a CLL patient with red blood cell issues, RBC can be much lower than these healthy reference ranges. Over the years I have seen many thousands of patient CBC reports, people seem to like sending me stuff and ask me to read the tea-leaves. I have seen RBC numbers as low as 1.5 to 1.0 Later in this article we will discuss some of the specific reasons why RBC can be low in CLL patients.
Hemoglobin (Hg, Hgb or Hb)
As we discussed above, hemoglobin is the crucial oxygen carrier in red blood cells. Take out all the water in the red blood cells and pretty much the only thing left is hemoglobin. Women tend to have slightly lower amounts of hemoglobin than men. In my case, the hemoglobin level is a tad low, below the reference range for my lab and hence it is flagged. I am a bit anemic, possibly due to low level of iron in my food (I am a vegetarian) and poor absorption of what iron there is in my diet due to early stage Crohn’s disease.
Anemia is easy to diagnose but not as easy to explain since it can be caused by many different things. Below is a chart of reasons why hemoglobin can be too high or too low. Remember, just because you have CLL does not give you a pass, a get-out-of-jail-free card from all the other things that go wrong with people as they age.
Remember this picture from our previous article? We said if you take a tube of fresh blood and spin it around fast in a centrifuge, the red blood cells will settle to the bottom and that this layer is just under half the volume of blood in the tube. Hematocrit is the volume of red blood cells in a sample of blood, reported as a percentage. A low hematocrit usually indicates decreased production, excessive loss, or destruction of red blood cells.
These three parameters, RBC, Hg and HCT, are the really important numbers as far as red blood cells are concerned. I tracked them for my husband for more than 8 years. MCV, MCH, MCHC are generally not as important (nevertheless, I have given short thumbnail descriptions of each of them below)
Once again, I cannot over emphasize the importance of not getting fixated on any one number but looking for overall trends. The important thing is to know what is a normal level of RBC, hemoglobin and hematocrit for you – since each individual is slightly different in what is normal for him or her – then to look for trends that are not just a fluke or bigger than usual lab error.
MCV (mean corpuscular volume)
The MCV measure the average size of the red blood cells in the sample. There is a range of sizes in red blood cells, not all of them are exact copies of each other. For example, newly minted red blood cells are just a bit bigger than older RBC that have been around the block more than a few times. Cell size can also change depending on dietary issues – B12 and folic acid deficient red blood cells are larger than iron deficient cells.
MCH (mean corpuscular hemoglobin)
The amount of hemoglobin in a single red blood cell is indicated by the MCH. It is a derived number, you can calculate MCH by dividing the total amount of hemoglobin by the number of RBC, then multiply by ten to make the units work. As you would expect, since my hemoglobin level is low, so too is my MCH.
MCH = (hemoglobin / RBC) x 10
MCHC (mean corpuscular hemoglobin concentration)
MCHC is the average hemoglobin concentration of packed red cells expressed as a percentage. You can calculate it by dividing the total amount of hemoglobin by the hematocrit, multiply by 100 to get percentage. Once again as you would expect, since my hemoglobin is on the low side, so too is my MCHC.
MCHC = (hemoglobin / hematocrit) x 100
RDW (red blood cell distribution width)
This number is kind of interesting. Remember, we said newly minted red blood cells are slightly larger than old ones. If there is a robust number of new red blood cells being made, as well as old ones hanging around, RDW will be a high number because the range of sizes of the cells present is broad. A small RDW number suggests there is no extraordinary amount of red blood cells being made in the bone marrow.
In CLL patients with sharply lower RBC – perhaps because of AIHA or some of the other reasons discussed below, the bone marrow will register this fact and try to compensate by producing more red blood cells to replace the ones being lost. If this is the case, a low RBC will be matched by a high RDW. But what if the RBC is quite low and the RDW does not show any tendency to increase? This may suggest that in spite of the obvious and crying need for increased production of red blood cells, the bone marrow is not able to oblige. Perhaps the marrow is choke full of CLL cells and with the best of intentions the marrow cannot produce new red blood cells because of the infiltration, or perhaps the bone marrow is just not getting the message. More about this further down.
Causes of Anemia in CLL, Our ‘Special Blessings’
There are specific reasons for anemia in CLL, over and above the general reasons (poor diet, physical blood loss etc) discussed above.
- Bone marrow infiltration. Bone marrow is the only site where new red blood cells can be made. If there are so many CLL cells in the bone marrow that the ‘factory’ is packed to the rafters with these cancerous cells, there is no room left for healthy production of other cells to make up for losses due to normal wear and tear. The remedy is to clean out the bone marrow with appropriate therapy to kill the CLL cells there.
- Bone marrow damage. Many of the chemotherapy drugs used to treat CLL are “myelosuppressive” – meaning they damage or reduce the production capacity of stem cells to produce more myeloid cells – red blood cells are part of the myeloid line. If the damage is temporary in nature, production will gradually recover and RBC counts will head back up gradually. Be patient, ride it out.
- Irreversible damage to hematopoietic stem cells is dangerous. The only choices at that point are stem cell transplant with healthy stem cells from a willing donor, or a lifetime of blood transfusion dependency.
- Lack of sufficient growth factor (erythropoietin). These are chemical messengers that alert the bone marrow to low RBC; marching orders as it were, that tell the marrow to gear up and increase production. No growth factor, no production. We are fortunate to have access to man-made epo drugs in recent years. But overuse of epo drugs carries its own penalties. Please read our earlier articles “Dark side of epo”
- Autoimmune disease. One of the most common autoimmune diseases in CLL is AIHA (autoimmune hemolytic anemia), where perfectly good red blood cells are targeted and destroyed by the body’s own immune system gone berserk. AIHA can be detected by Direct Coombs test and looking for antibodies targeting red blood cells. Treatment options include prednisone, Rituxan, chemotherapy drugs, spleen removal – some or all of the above, as it becomes necessary. Uncontrolled and severe AIHA can become life threatening all by itself.
Anemia symptoms are hard to miss. You will notice a significant drop in quality of life, no kidding. Below is a diagram that highlights some of the obvious ones.
Red Blood Cell Transfusions
Sometimes it becomes necessary to stabilize patients with transfusions if the RBC and / or hemoglobin levels get dangerously low. Each institution has its own policies about when to initiate transfusions. While getting any blood product carries some risk of infection, this risk can be minimized by taking proper precautions.
When the problem is too few red blood cells, patients are transfused with “packed red cells” – not whole blood. The red blood cells are separated from blood plasma and from the other cells such as platelets, white blood cells etc by simple process of centrifugation. This step concentrates the red blood cells so that they occupy less space, thus the term “packed.” A simple precaution is making sure the bag of packed cells your loved one is getting matches his/her blood type.
The risk of infection using standard issue packed red cells is trace levels of viruses (hepatitis is one of the biggest risk factors) that can hide out in the donor white blood cells. So, most blood banks recommend using irradiated and leukoreduced blood products for transplant patients as well as patients with any level of immune dysfunction. Leukoreduced means they put the packed red blood cells through another step of purification, where the last remnants of white blood cells (“leukocytes”) are removed, since viruses hang out in white blood cells. Irradiation is another step to increase the safety factor.
Irradiated and leukoreduced blood products are a tad more expensive than the garden variety blood products, but not prohibitively so, and definitely not as expensive as the complications patients can run into if the wrong products are used. I had reason to learn all about this while my husband was going through his stem cell transplant and needed frequent transfusions. You can read the details by visiting “Harvey’s Journal”, the on-line blog we maintained so others can learn from our experience through this difficult period of our lives.
As with most things, too frequent red blood cell transfusions carry the risk of iron overload. Each of those healthy new red blood cells coming into the body carries its own iron atom, and too many transfusions can cause too much accumulation of iron in the body of the patient. But this is not something to worry about unless we are talking of patients who are chronically transfusion dependant.