Complete Blood Count (CBC) Interpretation

Neutrophils are the first WBC to arrive at an area of inflammation. They begin working to clear the area of cellular debris through phagocytosis. Phagocytosis is the digestion of cellular debris by encapsulating foreign organisms and destroying them. Neutrophils are the most populous of the circulating white cells; they are also the most short-lived in circulation. After production and release by the marrow, they only circulate for about eight hours before proceeding to the tissues where they live for about 4 days. They are produced as a response to acute body stress, whether from infection, infarction, trauma, emotional distress, or other noxious stimuli.  When called to a site of injury, they phagocytose invaders and other undesirable substances and usually kill themselves in the act of doing in the bad guys.

Normally, the circulating neutrophils consist only of band neutrophils and segmented neutrophils, the latter being the most mature type. They are distinguishable by their segmented appearance, thus they are often called segs. Immature neutrophils, which are non-segmented, are known as bands. In stress situations (i.e., the acute phase reaction), the body reacts quickly by releasing the neutrophils before they have reached maturity. When this increase in bands is found, it is known as a shift to the left. As the infection or inflammation resolves and the immature neutrophils are replaced with mature cells, the return to normal is called a shift to the right. This term is also used to mean that the cells have more than the usual number of nuclear segments. This may be seen in liver disease, pernicious anemia, megaloblastic anemia and Down’s syndrome. The band count has been used as an indicator of acute stress. In practice, band counts tend to be less than reliable due to tremendous interobserver variability, even among seasoned medical technologists, in discriminating bands from segs by microscopy. Other morphologic clues to acute stress include the development of deep blue cytoplasmic granules, vacuoles, and vague blue cytoplasmic inclusions called Döhle bodies, which consist of aggregates of ribosomes and endoplasmic reticulum. All of these features are easily seen (except possibly the Döhle bodies), even by neophytes.

The normal range for a neutrophil (band + seg) count is 1160 – 8300/µL for blacks and 1700 – 8100/µL for other groups. This is 45%-74% segs and 0% - 4% bands. Obesity and cigarette smoking are associated an increased neutrophil count. It is estimated that for each pack per day of cigarettes smoked, the granulocyte count may be expected to rise by 1000/µL.

Monocytes which live months or even years are not considered phagocytic cells. However, after they are present in the tissues for several hours, monocytes mature into macrophages, which are phagocytic cells. These large cells are actually more closely related to neutrophils than are the other granulocytes.  Monocytes and neutrophils share the same stem cell. They are produced by the marrow, circulate for five to eight days, and then enter the tissues where they are mysteriously transformed into histiocytes. Here they serve as the welcome wagon for any outside invaders and are capable of processing foreign antigens and presenting them to the immunocompetent lymphocytes. They are also capable of the more brutal activity of phagocytosis. Unlike neutrophils, histiocytes can usually survive the phagocytosis of microbes. What they trade off is killing power. For instance, mycobacteria can live in histiocytes (following phagocytosis) for years. The normal range for the monocyte count is 200 – 950/µL or 4% - 10%.

Eosinophils play an important role in the defense against parasitic infections. They also phagocytize cell debris, but to a lesser degree than neutrophils, and do so in the later stages of inflammation. They are also active in allergic reactions. Current thinking is that eosinophils and neutrophils are derived from different stem cells, which are not distinguishable from each other by currently available techniques of examination. Although the hallmark of the eosinophil is the presence of bright orange, large, refractile granules, another feature helpful in identifying them (especially on H&E-stained routine histologic sections) is that they rarely have more than two nuclear lobes (unlike the neutrophil, which usually has three or four).  The normal range of the absolute eosinophil count is 0 – 450/µL or 0% - 7%.

Eosinophils are capable of amoeboid motion (in response to chemotactic substances released by bacteria and components of the complement system) and phagocytosis.  Since they are often seen at the site of invasive parasitic infestations and allergic (immediate hypersensitivity) responses, individuals with chronic allergic conditions (such as atopic rhinitis or extrinsic asthma) typically have elevated circulating eosinophil counts. The eosinophils may serve a critical function in mitigating allergic responses, since they can 1) inactivate slow reacting substance of anaphylaxis (SRS-A), 2) neutralize histamine, and 3) inhibit mast cell degranulation. The life span of eosinophils in the peripheral blood is about the same as that of neutrophils. Following a classic acute phase reaction, as the granulocyte count in the peripheral blood drops, the eosinophil count temporarily rises.

Basophils release histamine, bradykinin, and serotonin when activated by injury or infection. These substances are important to the inflammatory process since they increase capillary permeability and thus increase the blood flow to the affected area. Basophils are also involved in producing allergic responses. In addition, the granules on the surface of basophils secrete the natural anticoagulating substance, heparin. This provides some balance to the clotting and coagulation pathways. The most aesthetically pleasing of all the leukocytes, the basophils are also the least numerous, the normal range of their count in peripheral blood being 0 – 200/µL or 0% - 2%.  They are easily recognized by their very large, deep purple cytoplasmic granules which overlie, as well as flank, the nucleus. Eosinophil granules, by contrast, only flank the nucleus but do not overlie it.  It is tempting to assume that the basophil and the mast cell are the blood and tissue versions, respectively, of the same cell type. Actually it is controversial as to whether this concept is true or whether these are two different cell types.

In active allergic reactions, blood basophils decrease in number, while tissue mast cells increase. This reciprocal relationship suggests that they represent the same cell type (i.e., an allergen stimulates the passage of the cells from the blood to the site of the allergen in the tissues). Some experiments with animals have also shown that mast cells are marrow-derived and are capable of differentiating into cells that resemble basophils. Conversely, some recent evidence suggests that basophils (as well as eosinophils) can differentiate from metachromatic precursor cells that reside among epithelial cells in the nasal mucosa. The mast cell is the essential effector of immediate (Type 1) hypersensitivity reactions, which produce only misery, dysfunction, and occasionally death for the hapless host.

The immune WBCs, which include the T lymphocytes, or T cells, and the B lymphocytes or B cells, mature in lymphoid tissue (thalamus and bursa) and migrate between the blood and lymph system. They play an integral part in the antibody response to antigens. The lymphocytes have a lifespan of days or years, depending on their type. In the immune/inflammatory response, if the neutrophils and monocytes are the brutes, the lymphocytes are the brains. The functions of lymphocytes are diverse and complex. 

After neutrophils, lymphocytes are the most numerous of the circulating leukocytes. The normal range of the lymphocyte count is 1000 – 4800/µL or 16% - 45%. Unlike neutrophils, monocytes, and eosinophils, the lymphocytes 1) can move back and forth between the vessels and the extravascular tissues, 2) are capable of reverting to blast-like cells, and 3) when so transformed, can multiply as the immunologic need arises.

In normal people, most of lymphocytes are small, innocent-looking round cells with heavily painted-on nuclear chromatin, scant watery cytoplasm, and no granules. A small proportion of normal lymphs is larger and has more opaque, busy-looking cytoplasm and slightly irregular nuclei. Some of these have a few large, dark blue granules, the so called azurophilic cells (i.e., T-cells that have a surface receptor for the IgG Fc region) or natural killer (NK) null-cells.  Other phenotypes of lymphocytes are not recognizable as such on the routine WBC count. Special techniques are required for identification.

When activated, lymphocytes can become very large and basophilic; reflecting the increased amount of synthesized cytoplasmic RNA and protein.  The cytoplasm becomes finely granular, reflecting increased numbers of organelles, and the nuclear chromatin becomes less clumped. Such cells are called transformed lymphocytes, atypical lymphocytes, or viral lymphocytes by various votaries of blood smears. Although such cells are classically associated with viral infection, particularly infections mononucleosis, they may also be seen in bacterial and other infections and in allergic conditions.  A morphologic pitfall is mistaking them for monocytes (a harmless mistake) or leukemic blasts (not so harmless).

It is possible to observe the horror of life without lymphocyte function by studying the unfortunate few with hereditary, X-linked, severe combined immune deficiency. Such individuals uniformly die of systemic infections at an early age (except for the bubble boys of yesteryear, who lived out their short lives in antiseptic prisons).

• Stress, excitement, exercise, and labor may increase neutrophils
• Eosinophil counts are lowest in the morning
• Stressful conditions can decrease the eosinophil count
• Drugs that increase the number of basophils: antithyroid therapy
• Drugs that decrease the number of basophils: antineoplastic agents, glucocorticoids
• Drugs that increase the number of eosinophils: digitals, heparin, penicillin, propranolol hydrochloride, streptomycin and tryptophan
• Drugs that decrease the number of eosinophils: corticosteroids
• Drugs that decrease the number of lymphocytes: glucocorticoids, immunosuppressive agents
• Drugs that decrease the number of monocytes: glucocorticoids, immunosuppressive agents
• Drugs that increase the number of neutrophils: endotoxin, epinephrine, heparin, histamine, steroids
• Drugs that decrease the number of neutrophils: analgesics, antibiotics, antineoplastic agents, antithyroid drugs, phenothiazines, sulfonamides

The RBC count is also known as the erythrocyte count. It simply involves counting the number of RBCs per unit volume of whole blood.  Manual methods using the hemocytometer have been universally replaced by automated counting.  The result of the test is expressed as number of cells per unit volume, specifically cells/µL.  A typical lab’s normal range is 4.2 – 5.4 x 106/µL for females; for adults males it is 4.7 – 6.1 x 106/µL.

If the number of RBCs is decreased at least 10% below normal, the condition is known as anemia. There are several different types of anemia, with additional testing needed to differentiate among the various types. Like the WBC, more than one type of cell is included in this count. Unlike the WBC, RBC typing is a factor of age, not lineage or function. Some RBCs belong to a group called reticulocytes. These are young RBCs released into the bloodstream within the last 48 hours. Reticulocytes are identified by their large size and the presence of proteins not found in mature RBCs. Reticulocytes are normally released into the bloodstream at the same rate at which old RBCs are destroyed, about 1% of the total RBC component per day.  When the total RBC count, both young and old cells, is below 4.5 million for men and 4 million for women, the criterion for anemia is met.

Clinical laboratories measure several important parameters that reflect RBC structure and function. These measurements are used to 1) evaluate the adequacy of oxygen delivery to the tissues, at least as is related to hematologic factors and 2) detect abnormalities in RBC size and shape that may provide clues to the diagnosis of a variety of hematologic conditions. Most of these tests are performed using automated equipment to analyze a simple venipuncture sample collected in a universal lavender (or purple) top tube containing EDTA as an anticoagulant. Normal value is 4.15 – 4.90 x 106/mm3. Hemolysis of the sample may alter test results. False low results have occurred in the presence of cold agglutinins. Drugs that might increase the RBC count are gentamicin and methyldopa. Drugs that might decrease the RBC count are acetaminophen, aminosalicylic acid, ampicillin, antineoplastic agents, chloramphenicol, indomethacin, isoniazid, Phenobarbital, phenytoin, rifampin, tetracyclines, thiazide diuretics, and vitamin A.

Hematocrit (Hct) is a measure of the total volume of the erythrocytes relative to the total volume of whole blood in a sample. This is also called the packed cell volume or PCV. The result is expressed as a proportion, either unit less (e.g., 0.42) or with volume units (e.g., 0.42 L/L, or 42 cL/L [centiliters/liter]). The volume of individual erythrocytes can be electronically determined by measurement of their electrical impedance or their light-scattering properties. The normal range is 0.37 – 0.47 L/L for females, and 0.42 – 0.52 L/L for males. After collection of the sample, the specimen is centrifuged. Because of their weight, the RBCs are forced to the bottom of the test tube. A determination of these packed cells in comparison to the plasma is then made. The Hct indirectly measures the RBC mass, and the results are expressed as a percentage by volume of packed red cells in whole blood.  For example, if the test tube has 3 cm of RBC sediment and 7 cm of clear plasma above it, the Hct is 30%. If there were 4cm of RBC volume and 6 cm of plasma, the Hct would be 40%. Modern automated counters now calculate the sediment volume as the product of RBC number and size, making this ruler method obsolete, but the concept is unchanged. The Hct is still reported as the percentage of RBC volume in a sample.

Hct can be used to assess the extent of a patient’s blood loss. A drop of 3% in Hct equals approximately one unit of blood loss. It is important to note, however that the drop in Hct does not occur immediately. During an acute hemorrhage, the Hct is a source of deception, making the Hct an unreliable indicator of an acute bleed. As a result of a large blood loss, there is a loss of equal proportions of RBCs and plasma. Thus the Hct remains normal for a period of time. In an attempt to compensate for the blood loss and return the plasma volume to normal, the body shifts fluid from the intracellular and interstitial compartments to the intravascular compartment. RBCs, however, are not able to be replaced in such a short time. The relative percentage of RBCs, as denoted by the Hct, will decrease.

The Hct reflects the interplay of three variables: fluid volume, RBC count, and RBC size. Any one of these variables alone is enough to shift the Hct. For example, the Hct can help evaluate a patient’s fluid status. If fluid was added in the above test tube, as if the sample were drawn from a patient with fluid overload, the sediment volume percentage would obviously decrease, lowering the Hct. Conversely, removing fluid from the test tube, as if the sample were drawn from a dehydrated patient, would raise the Hct. In both cases, the absolute number or size of RBCs remains unchanged; only the fluid has been manipulated. Hct is a useful measure only if the patient’s hydration level is normal. When normal hydration is present and the total RBC count and hemoglobin are both normal, the Hct is approximately three times the hemoglobin result.

Another way to shift the Hct is to hold the fluid volume and RBC count steady, while changing the size of the RBCs. For instance, a collection of many small RBCs can have the same volume (and the same Hct) as fewer, larger ones. A good example of shifting by manipulating RBC size occurs with patients with diabetes. If one pours glucose into our conceptual test tube, simulating diabetic hyperglycemia, the red sediment will swell up, thus raising the Hct even though the fluid volume and RBC count is unchanged. This happens because glucose is transported into RBCs against a gradient. The higher internal concentration of glucose, relative to the plasma, pulls in water and makes the RBCs swell. This phenomenon, called hyperglycemic macrocytosis, discovered in 1985, can be a source of error in readings reported by automated cell counters. 

Any condition that increases the red cell count will increase the Hct such as burns, dehydration and shock whereas any condition that decreases the red cell count will decrease the Hct as in anemia and overhydration. Newborns have increase hematocrits. Because of the interplay among the possible variables that may impact the Hct, clinicians should always evaluate the patient history, clinical picture, and other CBC values along with the Hct.

Hemoglobin (Hgb) is the main component of erythrocytes, which serves as the vehicle for the transport of oxygen and carbon dioxide.  Hgb is composed of two portions. The heme portion contains iron and the red pigment pophyrin, and the globin portion is composed of amino acids that form a single protein called globin. The iron pigment combines readily with oxygen and gives blood its characteristic red color. The Hgb value on a lab report is a weight measure of how much Hgb in grams is in 100 mL of the patient’s blood. 

By measuring the Hgb concentration of the blood, one is determining the oxygen carrying capacity of the blood. This test is usually used to assess anemias. When the patient’s hydration status is normal, the Hgb is approximately one third of the Hct value. The normal range for Hgb is highly age and sex dependent, with men having higher values than women. Adults have higher values than children, except neonates, which have the highest values of all. For a typical clinical lab, the young adult female normal range is 12-16 g/dL; for adult males it is 14 – 18 g/dL. A value less than 14 g for men, or 12 g for women, is considered anemic. This is an easy test to perform, as Hgb is present in the blood in higher concentration than that of any other measured substance in laboratory medicine. The result is traditionally expressed as unit mass per volume specifically grams per deciliter (g/dL).

The Hgb component of the RBC transports gases that the lungs exchange, much like an extension of the respiratory system.  In fact, when the Hgb is low, the signs and symptoms of the patient are often directly related to the extent and severity of tissue hypoxia, as in a true respiratory depression. In the case of hemorrhage, an acute loss of Hgb is like an abrupt loss of partial lung function, because both situations reduce in the body’s ability to deliver oxygen to the tissues.  For this reason, anemias require oxygen support.

The Hgb rises when the number of RBCs increases. The Hgb falls to less than normal, indicating anemia, when the body decreases its production of RBCs or increases its destruction of RBCs, or if blood is lost due to bleeding.

The MCV is the mean volume of all the erythrocytes counted in the sample. The value is expressed in volume units, in this case very small ones, femtoliters (fL, 10-15 liter).  The normal range is 8 - 94 fL.  The formula for the calculation in general terms is:

MCV = Hct ÷ RBC count

As a measure of RBC size, it has only three possible findings:  microcytic, macrocytic, and normocytic.  Normocytic refers to blood with normal MCV.  One of these designations becomes the first term when classifying an anemia. For example, Microcytic anemia means the MCV is low.

A low MCV, or microcytic anemia, results most commonly from iron deficiency, the most common cause in the US and worldwide. Microcytic anemia is also caused by beta-thalassemia minor, the most common hemolytic disorder. Differentiating these two is vital.  Although these two potential causes may have identical Hgb and Hct values, the treatments are entirely different. One simple formula to differentiate the causes of microcytic anemia is the Mentzer index. This index uses the CBC values alone. If the red cells are microcytic, divide the MCV by the RBC. If the result is more than 13, the Mentzer index predicts an iron deficiency; if less than 13, the prediction is toward beta-thalassemia minor.

Iron-deficiency anemia is attributed to chronic blood loss until proven otherwise. With this in mind, the Mentzer index can guide a nurse’s thinking in certain patient care situations. For instance, a Mentzer index above 13 in a microcytic anemia might prompt a clinician to look for a source of chronic blood loss. An index of less than 13 might cause one to question any order to transfuse or to administer iron, since the patient may be not losing blood or needing iron.

A high MCV can result from many possible causes, but the big three are chronic alcohol abuse (by far the most common) and deficiencies of either folic acid or vitamin B12. Although folic acid and B12 deficiencies can produce identical anemias, even to the trained eye and under a microscope, mistreating them can have dire consequences.

If a B12 is misdiagnosed and treated as a folic acid deficiency, the MCV falls to normal, and all signs of anemia vanish. On the surface the situation may appear to be resolved, but irreversible neurological damage can result as the patient develops psychosis, ataxia, and neurological deficits that can mimic multiple sclerosis.  For these reasons, providers give both B12 and folic acid supplements to patients with macrocytic anemia when the specific cause is not known. Due to the serious consequences of a misdiagnosis here, nurses should question any order that offers only folic acid to correct an elevated MCV.  For patients with an elevated MCV, nurses should also assess for decreased vibratory sensation in the lower extremities and yellow-blue color blindness, two findings highly suggestive of B12 deficit and precursors of more severe, permanent neurological damage.

Keep in mind that the MCV measures only average cell volume. The MCV can be normal while the individual red cells of the population vary wildly in volume from one to the next. Such an abnormal variation in cell volume is called anisocytosis. Some machines can measure the degree of anisocytosis by use of a parameter called the red cell distribution width (RDW). This is simply a standardized parameter (similar to the standard deviation) for mathematically expressing magnitude of dispersion of a population about a mean. The normal range for RDW is 11.5% - 14.5%.

The RDW describes the volume variation in size among all the red cells in a sample. One might think that his function is already contained in the MCV, but it is not. The MCV describes a single, fictitious mean red cell, telling us its size.  The RDW describes the variance in the actual size of all the red cells. If a sample holds both microcytic and macrocytic cells, the MCV may be normal. In other words, the mean may mask the extremes. The RDW is not masked in this manner, but rises with variation, describing the group as a whole instead of one hypothetical cell.

An increased RDW can occur during reticulocytosis, which can arise in response to hemorrhage or a hemolytic disorder. A compensatory influx of large, young reticulocytes increases the width variance among the entire RBC population. The MCV, in contrast, would not shift as rapidly; the influx of a few million reticulocytes, diluted in the body’s total RBC volume, would not significantly increase the MCV.

The MCH represents the mean mass of Hgb in the RBC. In other words MCH measures how much (weight) Hgb there is in the RBC. The MCH is derived by dividing the Hgb by the RBC. The three possible findings are hypochromic, normochromic, and hyperchromic, meaning there is either too little, the correct amount, or too much Hgb in the average RBC. One of these designations becomes the second term when classifying an anemia.  For example, a microcytic, hypochromic anemia would mean that the red cells are small and low on Hgb. The formula for the calculation in general terms is:

MCH = (Hgb [in g/dL] x 10 ÷ (RBC count [in millions/µL])

Since small cells have less Hgb than large cells, variation in the MCH tends to track along with that of the MCV. The MCH is something of a minor leaguer among the indices in that it adds little information independent of the MCV. This value is helpful in pinpointing the source of an anemia.  A hypochromic anemia suggests an iron deficiency, chronic blood loss, or thalassemia. A normochromic anemia is associated with acute blood loss, renal or bone marrow failure, and hypometabolic states. Hyperchromic anemias may be found with alcoholism, folic acid or B12 deficits, and estrogen administration.

This is the mean concentration of Hgb in the red cell. Since whole blood is about one-half cells by volume, and all of the Hgb is confined to the cells, you would correctly expect the MCHC to be roughly twice the value for Hgb in whole blood and to be expressed in the same units; the normal range is 32 – 36 g/dL.  The value is calculated using the formula,

MCHC [in g/dL] = Hgb [in g/dL] ÷ Hct [in L/L]

Cells with normal, high, and low MCHC are referred to as normochromic, hyperchromic, and hypochromic, respectively. These terms have importance in anemia classification.  The MCHC is derived by dividing either the Hgb by the Hct or the MCH by the MCV. Both formulas should yield the same value, which is converted to a percentage that is roughly 33%. Knowing the relationships that can define the MCHC clarifies its value. The MCHC not only quantifies acute fluctuations in the over all Hgb and Hct, but also the chronic changes that occur at the level of one typical red cell, the mean red cell reflected in the MCH and MCV. The Hgb and Hct can shift by the hour, yet the MCV and MCH may take days or weeks to move. Nevertheless, both relationships yield the same MCHC value. This occurs because the MCV and MCH describe the mean, individual RBC. Normally, the morphology and composition of this single hypothetical cell should generalize to all red cells, so that properties that characterize the mean (MCH/MCV) should also describe the whole (Hgb/Hct).

Just as the MCH measures how much Hgb there is, the MCHC measures how tightly the Hgb is packed within a RBC. Together these two values yield important clues to the nature of a hematological disturbance. For example, consider a lab report showing a high MCHC (density) combined with a high MCH (weight), a finding commonly found in only two situations, estrogen administration and the genetic disease spherocytosis. A high MCHC and a high MCH due to estrogen administration occurs with only a high MCV; this occurrence due to spherocytosis occurs with only a low MCV.  The precise narrowing of thousands of possible causes to one probable cause is possible because of the relationship of the MCHC to the MCH and MCV.