Understanding The CBC for Clinical Practice

THE COMPLETE BLOOD COUNT

 The CBC is the most basic of the labs that we order. It is a primary screener of disease and a basic monitoring of the patient. The CBC gives an idea of the body’s response to stress, the body’s oxygen carrying capacities as well as giving a platelet count, which reveals how well the blood is clotting.

There are two main elements that we need to evaluate when looking at a CBC. We are going to look at the formed elements, which are red blood cells, white blood cells and platelets, and we are also going to look at the indices, which are used to describe the red blood cell count and then give us a idea of possible disease.

When we talk about the formed elements, let’s start off talking about the white blood cell, also known as a leukocyte, where an abnormal elevation of white blood cells is referred to as a leukocytosis, and an abnormally low white blood cell count is referred to as leukopenia. There are two reasons why we would have a leukocytosis, and it is really best to find whether there is an infectious problem or a noninfectious problem. There are three ways to gauge infection from a CBC. We are concerned with the absolute number of white blood cells, the percentage of neutrophils and the number of immature cells. The absolute number of white blood cells means the total number of white blood cells. A normal value is between 5,000 and 10,000.

When we look at someone for an infection, the first thing we are going to look at is the absolute number. Is this a white count of 12,000, or 14,000, or 24,000? That will give us a clue as to whether the cause of the problem is, indeed, infection.

When it comes to white blood cells, there are five different kinds. We have neutrophils, basophils, lymphocytes, monocytes, and eosinophils. Neutrophils encompass approximately 75% of all the white blood cells put together. So, neutrophils are the powerhouses that are in charge of the phagocytosis of bacteria. When we have a bacterial infection, neutrophils have a tendency to increase in number. So, when we denote a patient whom we feel has an infection, we would denote their absolute number of white blood cells, let’s say 17,000. Also, we would note the number of neutrophils. If a patient has a 17,000 white count and 90% neutrophils, it strongly suggests a bacterial infection. So, neutrophils are really the white blood cell count we are most interested in.

 Next, when I talk about immature cells being noted, I am talking about band cells. Band cells are immature white blood cells, and I like to suggest that they are similar to the United States Marines, which means if you see a bunch of United States Marines in a country, you know there has been a bad fight that has gone on, and normally the Marines are the first to go in, the first to fight. Band cells suggest that a pretty intense infection has been going on and has used up all the white blood cells (the neutrophils) that are available to the body and the body has had to call on immature cells to come in and help fight the battle. In summary, there are three ways to gauge infection from a CBC: the white blood cell count, the neutrophil count, and the band count.

Now, how do we work up infection? We have a patient who comes in that we believe may have some degree of infection, and classically this could be a nursing home patient who is demented and really cannot give us much of a history, or even a child who is sick, and may have an infection. So, how do we work up infection, and how do we use the white blood cell count to help us determine whether this is a patient has an infectious problem or noninfectious problem? The first step is

to use all resources available to get a good history, whether it is from nursing home staff or a parent. In addition to a thorough history, we need objective findings, including vital signs. We need to get a valid temperature, and the best way to do that is to get a rectal temperature. Axillary temperature and tympanic temperature are often inaccurate. Oral temperature could be valid if you have a compliant patient who can hold the thermometer under the tongue with their mouth closed. But still, there is variability in how that temperature is obtained. If you want the best, valid temperature, get a rectal temperature. Now, do I do that in all my patients? No, of course I don’t. If a 30-year-old female comes in with probable pneumonia, I don’t do a rectal temperature. But, as a medical provider you are solely responsible for your patient’s health, and the most valid way to know if they have a fever or not is with a rectal temperature. The second thing we have to consider is that 9 out of 10 infectious problems that would hit the average adult, or child, would be an infection in the wind or the water, wind being pneumonia and water being urine. You need to do a two-view chest x-ray and a urinalysis with culture.

Now, a two-view chest x-ray is important because we can see lower into the lungs and behind the heart, which may be missed on a one-view chest x-ray. So, always do a two-view chest x-  ray and a urine.

The second aspect of objective findings is the basic-screening labs. This would include first the white blood cell count where we would look at the absolute number, the number of neutrophils and the number of bands. Second would be blood cultures x2. Let’s focus on cultures. Staphylococcus is a very common germ that resides on our skin, in our nares, in our axilla and in our groin. When we do cultures on a person, we draw them from the arm, and if the blood cultures grow out staph, we would have to be concerned about whether this is a bacterial infection that is in the blood. So, is this patient bacteremic with staph or was it just a contamination from the skin? A way to avoid confusion is to get two sets of blood cultures by either drawing from two separate sites (having the nurse draw from the right arm and from the left arm) or drawing from the same site but half an hour apart. Blood cultures should be a provider’s knee-jerk response to working up infection. At times they may have a low clinical yield, but just do blood cultures anyways. From my experience, I have found myself in hot water at times working up infection where I did not do blood cultures initially. Now, this does have to do with hospital administration and with reimbursement costs. If you are working up someone for infection, especially pneumonia, do one set of blood cultures. It is important to get two sets of cultures when you think you have a patient who is truly septic, looks sick, has a high fever, borderline blood pressure and is shaking with rigors. If you really think the patient is sick then order blood cultures. Now, under those circumstances, you would not want to wait a half hour between blood draws because you would want to draw blood and get cultures quickly so you can get antibiotics on board. In that case, I would recommend using two different sites.

If nine out of ten infections are from wind or water, we have to be concerned with the abdomen and the cerebral spinal fluid as that one cause for infection. Let’s talk about the abdomen. Physical exam of the abdomen has to do with guarding, rebound and rigidity. In looking at the pathophysiology of the abdomen, there are the intestines, held in place by the peritoneum. When the peritoneum becomes irritated, it clamps down and clamps the muscle structures down. The only way to really get good at determining whether a patient has peritonitis (inflammation of the peritoneum) is by feeling a lot of bellies and feeling surgical bellies (a patient who has peritonitis).

Guarding is the response that occurs when, as you examine a patient’s belly, they voluntarily flex their stomach muscles so you cannot examine them. 

Rigidity is an unresponsive flexing of stomach muscles, where you cannot get him to relax or distract him so you can examine the belly because the muscles are constantly flexed. That is known as a rigid abdomen. Rebound tenderness has to do with actually shaking the peritoneum, and that shaking causes pain. Now, from the physical exam perspective, as I am sure you folks know, you push down on one part of the belly, you let go, and that motion vibrates the peritoneum which causes pain at the site of irritation. Another way to do this is to do a heel jar test. This is where I would approach a patient from the bedside, make a closed fist and actually strike the heel of the foot a number of times. This will shake the peritoneum and cause pain at the site of inflammation. From an historical perspective, this is where you would ask the patient, “Did every bump on the car ride over cause you pain?” You ask this because every bump that is hit on the drive over would vibrate the belly, again, causing a degree of rebound tenderness.

With regard to the abdominal exam, rebound, guarding and rigidity, when you are dealing with a patient who has diabetes or who is on chronic steroids, all bets on the physical exam are off. In a patient with diabetes, the nerves that integrate the peritoneum are kind of blunted, so they will not have normal physical exam findings. It is the same thing in a patient on chronic steroids.

When it comes to the cerebral spinal fluid, we should be very concerned about meningitis. Any patient that you evaluate for an infection, for the rest of your career, must be given a neck evaluation. A person coming in with a fever is very different than a person who comes in with a fever and a rigid neck.

Now, the neck exam of someone who has meningitis is not like someone who slept in a funny position and woke up having a sore neck. A rigid neck is when someone’s neck is board-like. They cannot turn their head to look over their shoulder without causing tremendous pain. Their body twists at the shoulders to compensate for that pain. Physical exam findings include Brudzinski sign, where you actually flex the neck bringing the chin down to the chest, which causes severe pain down the back. Kernig sign is when the patient is on their back, supine, and you have them flex at the knee and at the hip. When you extend at the knee, it causes severe pain in the lower back because it is pulling on the meninges. These are also known as meningeal signs.

The red blood cells have a lifespan of approximately 120 days. When we talk about red blood cells, we are concerned with three related values: the absolute number of red blood cells, the hemoglobin, and the hematocrit. Now, the absolute value of red blood cells is used to calculate hemoglobin and hematocrit, and it is the hemoglobin and hematocrit that we use to make clinical decisions. Out of the three numbers that we use to help us gauge a patient’s oxygen carrying capacity, we are really concerned with the hemoglobin and hematocrit, which are derived from the red blood cell count. Now, the hemoglobin is the oxygen-carrying component of a red blood cell, and it is measured in grams per deciliter. Normal is approximately 13 through 15. When the hematocrit is a measured percentage of a spun-down sample, a normal percentage is about 42 to 52%. Now, when it comes to hemoglobin to hematocrit, there is a very fixed ratio of 1:3, where if the hemoglobin is 10, the hematocrit is 30. Or, if the hemoglobin is 13, then the hematocrit is 39. Of interest is that some medical schools train people to really focus on one value when other medical schools train people to focus on the other. I am a hematocrit guy, and I think of patients in terms of hematocrit. If someone called me on the phone and said, “Hey, I’m sending in a patient who has a hemoglobin of 7,” I have a tough time relating that hemoglobin of 7 to clinical use. I have to convert this over to a hematocrit of 21, and then I will have a good idea of how a patient will look.  Other people will use hemoglobin, and if I tell them I have a patient with a hematocrit of 30, they are going to translate over to hemoglobin. So, with that said, when you are in a hospital or when you are working with a physician, use both. Give them the hemoglobin and hematocrit even though they both kind of are relative to each other, but different people think in terms of different numbers.

When we look at red blood cells, we are really looking to see whether this patient has anemia. That is the primary reason why we look at the hemoglobin and hematocrit. Now, anemia is not a disease. It is a symptom of a disease. A little boy can have a fever, and that does not really tell you anything about how sick he is. It could just be a virus or could be bacterial pneumonia. It is the same thing with a patient who is anemic. Anemia is a sign of a disease, and we need to figure out why they have anemia. It shows a degree of not thinking through the disease properly if you just mention, “Hey, I have a patient who is anemic,” without saying why. Whether it is iron-deficiency anemia or a gastrointestinal bleed that is the cause. So, you should never in your career just say, “I have a patient who is anemic.” It is more helpful to say, “I have a patient with anemia of unknown etiology,” because you have not quite figured it out yet.

How will a patient with anemia look? As I have said earlier, a normal hematocrit value is between 42 and 50. So, if I ask the question, “How will a patient look with a hematocrit of 25, and what clinical findings would a patient have with a hematocrit of 25? The answer is, “It depends.” The symptoms of anemia are based on the onset or the rapidity, how rapid the onset was of the anemia. If you have someone who has sickle cell anemia and their anemia has developed over years, the body will have compensated very well for a hematocrit of 25, and these people could be a bit fatigued at times, but overall they go through their daily functions without any limitations. If somebody has been in a car accident and has lacerated their spleen, and they go from a hematocrit of 45 to 25 in a matter of an hour, they would be knocking on death’s door. So, when you say someone is anemic at 25, the symptoms of the anemia are based on the onset.

A question I am often asked by students is, “At what number do we do a blood transfusion on a patient?” My answer to this question is really not concrete. A rough gauge is to say a hematocrit of 25 (hemoglobin of 8), but that is really relative to how long it took the patient to get there and what signs and symptoms are present from anemia. So, this question we will answer more in the chapter when we talk specifically about blood transfusions. Understand that anemia and transfusion is more of an art than a science, and it is very practitioner-dependent. A surgeon may be very quick to transfuse at a hematocrit of 25, but an internist may be a whole lot more sluggish to do that, or even visa versa.

When we evaluate anemia, the most important thing we need to look at to determine what is causing the anemia is the size of the cell or the mean corpuscular volume (MCV). You can have small cells, you can have normal cells or you can have large cells, all dependent on the MCV. Normal MCV is between 81 and 97, so if you have an MCV of 70, you have small cells. An MCV of 105 indicates large cells. Let’s focus on microcytic anemia. Now, there are four main causes of microcytic anemia, and I hope these STIC with you.

The S stands for sideroblastic. This has to do with heavy metal ingestion such as lead. (When we are evaluating the relatively uncommon sideroblastic anemia, know that a buzzword on your board exam is “basophilic stippling.”)

The T stands for thalassemia, which would be diagnosed by hemoglobin electrophoresis. This is most often seen in people of Mediterranean descent and can be anything from a minor trait and relatively insignificant to the patient, to a major trait meaning they do not live a long life. The I is for iron- deficiency. The C stands for chronic disease. Anemia of chronic disease is more of a diagnosis of exclusion, and this may also be normocytic. As a patient ages and has multiple medical problems, they are found to have a degree of anemia, and when they are worked up, there is really no cause found. Therefore, providers will say, “Well, it is just anemia of chronic disease and pretty close to their baseline.”

The red blood cells are stimulated by erythropoietin. Know erythropoietin is created from the kidneys. A patient who has renal insufficiency or renal failure and is on dialysis will have very low erythropoietin levels and will be anemic. It is quite common for someone on dialysis to have anemia, secondary to decreased erythropoietin. Patients who are severely anemic from this etiology will receive erythropoietin shots from time to time.

The most common reason why someone would have microcytic anemia is from gastrointestinal bleeding. This could be from an ulcer in the stomach or duodenum or a polyp or a malignancy in the lower gastrointestinal tract. Now, the cells that are produced in response to bleeding come out smaller than the red blood cells that are there physiologically. When we are concerned a patient has gastrointestinal bleeding, the first thing we have to do is a rectal exam. If this is positive for blood, then a lot of our work up is done and we can refer on to the gastroenterologist.

To clinch the diagnosis of gastrointestinal bleeding, there are a couple of tests that we can look at on the CBC that would be helpful. The first one is the MCV. Now, the mean corpuscular volume again has to do with the size of the cells. As I have stated before, the red blood cell’s lifespan is 120 days. So,

just for the purpose of understanding, let’s say it is about 100 days; we could make the assumption that every day 1% of our red blood cells are turned over. Now if someone is having gastrointestinal bleeding, the cells that are produced in response to the bleeding come out smaller.

The MCV is an average of all the red blood cells. If you have someone who has been bleeding for 10 days, it means 10% of their cells are going to be smaller, and the MCV will not have changed. It will still look normalized because 90% of the cells are of normal size. The MCV will not change to a microcytic state until approximately half the cells are small. So, if half the cells would have to be small to change the MCV, this bleeding (based on using 100 days as the lifespan) would take 50 days for the cells to become microcytic. Therefore, if you have someone who comes in with a microcytic anemia from gastrointestinal bleeding, it is safe to assume that this bleeding has been going on approximately two months or greater. If you have a young lady who comes in with vaginal bleeding that has been going on for two weeks, and you check the hemoglobin and hematocrit, which are 10 and 30, it is lower than her baseline. And, if the MCV is normal, it is consistent with someone who has had bleeding going on two weeks.

Another helpful test to determine if someone is having gastrointestinal bleeding is a reticulocyte count. A reticulocyte is an immature red blood cells and come out only when red blood cells are disappearing. This is either through gastrointestinal bleeding or hemolysis. Normally when you check someone’s blood, the reticulocyte count is approximately 1-2%. If someone is having gastrointestinal bleeding, or hemolysis, the reticulocyte count will be up to 4-5%. So, a helpful test to work up someone you presume is having gastrointestinal bleeding is a reticulocyte count. If this is high, they are having blood loss, and 49 out of 50 times, it is from gastrointestinal bleeding or some kind of bleeding. It is a relatively inexpensive test. It requires the lab technician to just stain the smear in a slightly different way. So, it is a helpful test and is relatively inexpensive.

Another part of the CBC that is helpful in working up a patient with anemia is the red blood cell distribution width (RDW). The RDW is a bit confusing. The bottom line is that it is helpful to determine early gastrointestinal bleeding. The red blood cell distribution width has to do with looking at the difference between the biggest cell and the smallest cell in giving you a percentage. Now, normally, someone who is not bleeding has a difference between their small cell and biggest cell at about 10%, so that is a normal variation; a normal red blood cell distribution width. As I said earlier, when someone is bleeding, the cells that come out in response to that bleeding will be disproportionally small. So, if you have a red blood cell distribution width that is 15 or 20%, it means the difference in the smallest cell to the biggest cell is higher than baseline and that suggests early gastrointestinal bleeding. So, if you have that girl who had vaginal bleeding for a week or two, and you check her H&H which is low, her MCV is normal, you can expect the RDW to be high. So, again, if we are using 1% turnover of red blood cells daily, after two weeks, you can assume that approximately 14% of her red blood cells would be small. Now, that is not enough to change the MCV to a microcytic status, but it is enough to enlarge the RDW. Now, here is a question for you? How will the reticulocyte count look in a girl who is having vaginal bleeding for the past two weeks? It would be elevated because of blood loss.

 Now let’s talk about macrocytic anemia. These are people who have large cells and who are anemic. In macrocytic anemia, the most common by far is B-12 or folate deficiency. If someone comes in with a macrocytic anemia, we have to check a B-12 and folate level. Also, this is a good time to pick up someone who is an alcoholic. These people can have what is called a “martini macrocytosis.” They have large cells, but may not always be anemic. If someone comes in with macrocytosis, you should be concerned that they have a history of excessive drinking in your differential. The liver has about two years of B12 stored in to get to that level. However, if someone comes in with folate deficiency, it can happen in about two months, or about the same time frame it takes to have a gastrointestinal bleed and become microcytic. So, folate can happen in about two months whereas B12 deficiency takes years.

In summary, a typical anemia work up is done in the following steps. If a patient is anemic, the first question we have to ask is, “How does the MCV look?” Do we have a patient who is microcytic, normocytic or macrocytic? If they are microcytic, order a reticulocyte count. If it is high, we know that they have blood loss, either hemolysis or gastrointestinal bleeding. We would also order iron studies and would have to do a rectal exam. A patient who comes in who is normocytic, you would need to do a reticulocyte count, do a rectal exam (this is where we would evaluate red blood cell distribution width to help us identify an early gastrointestinal bleed) and this would be a good time to check renal functions to see if this is someone with renal insufficiency and not secreting enough erythropoietin. With a patient who has a macrocytic anemia, we do a B12 and folate level, and we have to get a very good history about their drinking. Are they a daily drinker or are they a closet drinker? Just be aware that people who are heavy alcoholics will not come clean and admit the exact degree of what they drink, so do not hesitate to get the family involved in the questioning.

Finally, I would like to discuss the indices and describe the red blood cells. The MCV is the mean corpuscular volume, which is the size of the red blood cells. The MCV is the most important index when it comes to working up a patient with anemia. The next one is the mean corpuscular hemoglobin or MCH, which refers to the color of the cell and is of low clinical value. A patient who is microcytic almost always would be considered hypochromic (MCH means they have small cells that are a little more pale). So, mean corpuscular hemoglobin refers to color. You will hear people referred to as having a macrocytic hyperchromic anemia, which means they have big cells that are dark. Again, the fact that they are dark or light is really irrelevant. We want to know the MCV. Are they small or are they big? MCHC stands for mean corpuscular hemoglobin concentration. This has no clinical value and no decisions can really be made based on the MCHC. The RDW (red blood cell distribution width) can be used to help us diagnose early gastrointestinal bleeding. It is not an absolute test and does not make me hang my hat on a diagnosis, but it is a helpful test.

So, once again if someone comes in with a normocytic anemia and a high RDW, it suggests that the patient may be bleeding before the MCV has changed, and we really need to do rectal studies.

Questions about live CME conferences or video education from John Bielinski, CME4Life, The Emergency Medicine Institute or American Medical Seminars, email [email protected]