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Complete Blood Count (CBC) Interpretation

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Author:    Patricia Hartley (RNC, MSN)

Purpose/Goals

This course is intended to improve understanding of information provided in a standard complete blood count (CBC).

Objectives

Upon completion of this module the learner will:

  1. describe the relationships between components of a CBC,
  2. discuss the function of white blood cells (WBC),
  3. discuss the function of red blood cells (RBC),
  4. categorize common anemias based upon findings of the CBC, and
  5. discuss the importance of the RBC Indices.

Introduction

The complete blood cell count (CBC) with platelet count and differential count is one of the most commonly performed tests in health care. This is due to the vast amount of data obtained through the various components of this test. The CBC findings give valuable diagnostic information about the hematologic and other body systems, prognosis, response to treatment, and recovery.

The CBC is frequently ordered as part of a routine medical exam. If appropriate, the components of the CBC may be ordered as individual tests. The CBC consists of a series of tests that determine the number, variety, percentage, concentrations, and quality of blood cells. In most laboratories, these tests are completely automated. Historically, white blood cell (WBC) counts and red blood cell (RBC) counts were done by looking at cells smeared on a glass slide.

Blood is composed of a variety of living cells that circulate through the heart, arteries, and veins carrying nourishment, hormones, vitamins, antibodies, heat, and oxygen to the body’s tissues. Blood contains three main components: red blood cells (RBC), White Blood Cells (WBC), and platelets. These cells are suspended in fluid called plasma.

WBC

The purpose of WBCs is to protect the body from invasion by foreign substances such as bacteria, fungi, and viruses. All blood cells, including WBCs, originate from a common stem cell. Blood cell differentiation takes place in the bone marrow. This differentiation results in the development of the phagocytic WBCs and the immune WBCs.

The phagocytic WBCs include granulocytes and monocytes. Granulocytes are so named for their granular appearance. They are also called polymorphonuclear leukocytes (polys) because of their multilobed nucleus. The three types of granulocytes are neutrophils, eosinophils, and basophils. Monocytes, along with lymphocytes, are considered mononuclear leukocytes, since their nuclei are not multilobed. They have also been called agranulocytes since at one time it was thought that they had no granules on their surfaces. However, it is now know that their surfaces do contain extremely small granules.

CBC

The WBC count is a gross count of every cell in a blood sample that is not red, regardless of its cell type. It is the total number of WBCs in one cubic millimeter of blood. The WBC differential counts are the percentage of basophils, eosinophils, lymphocytes, monocytes and neutrophils within a sample of 100 WBCs. Since the differential percentages always equal 100%, an increase in the percentage of one type of WBC causes a mandatory decrease in the percentage of at least one other type of WBC.

The WBC count serves as a useful guide to the severity of a disease process. Specific patterns of leukocyte response can be determined by the differential count. The WBC count generally points to infectious processes, it does not indicate infection, nor does a low WBC ensure that there is not one.  Noninfectious factors, such as adverse effects of medications, trauma, air pollution, and even mental stress, can raise the WBC. On the other hand, dozens of infectious processes, from amebiasis to yellow fever, do not raise the WBC count at all. In fact, these infections may signal their presence by lowering it. The WBC is thus nonspecific, yet sensitive. Because so many factors can influence it, the WBC is a valuable indicator that something is wrong somewhere.

Providers often order a differential when an unusual WBC is noted and the clinical picture does not provide an adequate explanation. The differential breaks down the nonspecific WBCs into cell families. These cell lines respond differently to diverse insults and agents. Depending on which cell counts are raised, neutral, or lowered, the differential can help identify the source of an abnormal reading.

Each type of leukocyte has its own function and ontogeny, semi-independent of the others. WBC count has traditionally been considered a cardinal measurement in a routine laboratory workup for just about any condition to evaluate critically the hematologic status of a patient. Consider the individual absolute counts of each of the leukocyte types rather than the total WBC count with differential.  In many labs, the result will be reported as a relative differential, like this:

  • WBC                                       6000/µL
  • Segmented neutrophils        60%
  • Band neutrophils                   2%
  • Lymphocytes                         25%
  • Monocytes                             8%
  • Eosinophils                            3%
  • Basophils                               2%

Multiply the WBC count by each of the percentages given for the cell types; this gives absolute differential.  The illustration above becomes:

  • WBC                                       6000/µL
  • Segmented neutrophils        3600/µL
  • Band neutrophils                   120/µL
  • Lymphocytes                         1500/µL
  • Monocytes                             480/µL
  • Eosinophils                            180/µL
  • Basophils                               120/µ

The total WBC count is invariably done using an automated method.  The differential count may be done manually, using a microscope in smaller labs.  The automated methods are amazingly accurate, considering the fine distinctions that must often be made in discerning one type of leukocyte from the other. One manufacturer’s machine can quite reliably pick out one leukemic blast cell in eight hundred or more leukocytes.

Neutrophils

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

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

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

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.

Lymphocytes

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).

Contributing factors to abnormal WBC counts

  • 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

 

RBCs

The RBC consists of what is left after the white cells are excluded. It is the measure of the number of RBCs (erythrocytes) per cubic millimeter of blood. RBCs have a life span of 80-120 days and are produced by the bone marrow. The main function of the RBC is to carry oxygen from the lungs to the body tissues and to transfer carbon dioxide from the tissues to the lungs.

Structurally the simplest cell in the body, volumes have been written about the lowly RBC. In the normal state, erythrocytes are produced only in the skeleton; in adults only in the axial skeleton. However, almost any organ can become the site of erythropoiesis.  Numerous substances are necessary for creation of erythrocytes, including metals (iron, cobalt, manganese), vitamins (B12, B6, C, E, folate, riboflavin, pantothenic acid, thiamin), and amino acids.  Regulatory substances necessary for normal erythropoiesis include erythropoietin, thyroid hormones, and androgens. Erythrocytes progress from blast precursors in the marrow over a period of five days. Then they are released into the blood as reticulocytes, distinguishable from regular erythrocytes only with special supravital stains. The reticulocyte changes to an erythrocyte in one day and circulates for 120 days before being destroyed in the reticuloendothelial system.

RBC production is stimulated by erythropoietin, a hormone secreted by the kidneys. The amount of erythropoietin secreted increases whenever tissue hypoxia occurs. Such hypoxia occurs in individuals living at high altitudes. The result is the production of an increased number of RBCs; this is known as polycythemia.

Erythrocyte count

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.

Possible Meanings of Abnormal RBC Values

Increased

Decreased

 

 

Cardiovascular disease

Addison’s disease

Chronic lung disease

Anemias

Congenital heart defects

Bone marrow suppression

Cushing’s disease

Chronic infection

Hemoconcentration

Hemodilution

Hepatic cancer

Hodgkin’s disease

Polycythemia vera

Hypothyroidism

Renal cyst

Leukemia

Secondary polycythemia

Multiple myeloma

 

Rheumatic fever

 

Subacute bacterial endocarditis

 

Systemic lupus erythematosus

 

Vitamin deficiency (B6, B12, folic acid)

Hematocrit

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

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.

RBC Indices

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.

Mean corpuscular volume (MCV)

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.

Red Cell Distribution Width (RDW)

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.

Mean corpuscular Hgb (MCH)

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.

Mean corpuscular Hgb concentration (MCHC)

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.

Platelets

Platelets (thrombocytes) are the smallest of the formed elements in the blood.  They are fragments of megakaryocytes which are formed in the bone marrow. They circulate in the blood stream for a life span of 8 – 12 days, at which time they are removed from the circulation by the spleen. Platelets are essential to homeostasis and blood clotting. When a blood vessel wall is injured, the platelets adhere to its wall and aggregated, forming a platelet plug. Platelet activity is necessary for vascular integrity and vasoconstriction as well.  Platelets release phospholipids that are required by the intrinsic coagulation pathway. These cells are non-nucleated, round or oval, flattened, disk-shaped structures.  The normal platelet range count is 133 – 333 x 103/µL.

Platelets are counted by machine in most hospital labs and by direct phase microscopy in smaller facilities. Since platelets are easily mistaken for garbage and vice versa, by both techniques, the platelet count is probably the most inaccurate of all the routinely measured hematologic parameters. Actually, you can estimate the platelet count fairly accurately (up to an absolute value of about 500 x 103 /µL) by multiplying the average number of platelets per oil immersion field by a factor of 20,000. For instance, an average of ten platelets per oil immersion field (derived from the counting of ten fields) would translate to 200,000/µL (10 x 20,000).  Spontaneous bleeding of a minor nature and prolonged bleeding following surgery or trauma generally does not occur unless the platelet count is less than 30,000/µL, if the platelets function properly.  The most serious risk lies with patients whose platelet counts are fewer than 20,000/mm3. Screening for proper platelet function is accomplished by use of the bleeding time test.

Patients who have a bone marrow disease, such as leukemia or other cancer in the bone marrow, often experience excessive bleeding that is generally due to a significantly decreased number of platelets. This is called thrombocytopenia. Low numbers of platelets may occur in some patients with long-term bleeding problems because the supply of platelets is reduced. Individuals with an autoimmune disorder, where the body’s immune system attacks its own organs, can cause the destruction of platelets. Lupus is one such disorder. Patients undergoing chemotherapy may also have a decreased platelet count.

When bone marrow function declines, the megakaryocytes are small, resulting in small platelets. In response to blood vessel wall injury it is advantageous for the platelets to be large. If a condition other than bone marrow dysfunction is the cause of a low platelet count, the bone marrow tries to compensate by releasing larger platelets. Thus the measurement of the mean platelet volume assists in the diagnosis of thrombocytopenic disorders. The normal value for mean platelet volume is 25 micrometers in diameter.

More commonly, in up to 1% of the population easy bruising or bleeding may be due to an inherited disease called VonWillibrand’s disease.  While the platelets may be normal in number, their ability to stick together is impaired.  Many cases go undiagnosed due to the mild nature of the disease; however, the more severe form can be devastating.

Increased platelet counts, called thrombocytosis, may be seen in individuals who show no significant medical problems. Others may have a more significant blood disorder problem called myeloproliferative disorder which is an abnormal growth of blood cell elements

Platelet counts may be increased in high altitudes, persistent cold temperatures, strenuous exercise, excitement, and with drugs such as epinephrine and oral contraceptives. A platelet count may be decreased prior to menstruation or due to medications such as amphotericin B, ampicillin, and aspirin.

Other Cells in Blood

Plasma cells sometimes appear in the peripheral blood in states characterized by reactivity of lymphocytes. Old time hematologists often maintain that the cells that look exactly like plasma cells on the smear are really plasmacytoid lymphs. 

Endothelial cells occasionally get scooped up into the phlebotomy needle during blood collection and show up on the slide. They are high and tend to be present in groups. 

Histiocytes, complete with pseudopodia and phagocytic vacuoles, may appear in states of extreme reactivity, especially in septic neonates. Nucleated red cells may also be seen in small numbers in the peripheral blood of newborns. In adults, even a single nucleated RBC on the slide is abnormal, indicating some sort of serious marrow stress, from hemolytic anemia to metastatic cancer. 

Myeloblasts are always abnormal and usually indicate leukemia or an allied neoplastic disease. Rarely, they may be seen in non-neoplastic conditions, such as recovery from marrow shutdown (aplasia).  Later stages of myeloid development (promyelocyte, myelocyte, metamyelocyte) may be represented in the peripheral blood in both reactive states and leukemias.

Summary

The CBC is a basic, routine test that is not diagnostically specific in its individual values. It is the most commonly performed tests in health care due to the vast amount of data obtained through the various components. The CBC is a group of mostly interrelated tests that is meant to be examined as a whole and then correlated with the clinical picture. An infection can occur with a high WBC or a low one. Blood loss can present with or without a change in the Hgb and Hct. Blinding oneself to all that the CBC reveals, by narrowly focusing on only a few specific values, doesn’t begin to use the wealth of information it actually contains.

References

Brose, Marcia. (2003) Blood Differentials, Medical Encyclopedia, Medline Plus.

Browning, Randal H. (2004) CBC 101: Blood Count Basics, Nursing Spectrum.

Duffy, T. (2000) Approach to the patient with anemia. Kelley’s Textbook of Internal Medicine. 4th ed. Philadelphia, PA: Lippincott Williams Wilkins.

Kee, J. (2004) Handbook of Laboratory and Diagnostic Tests with Nursing Implications. 5th ed. Englewood Cliffs, NJ: Prentice Hall.

Wilson, Denise D. (1999) Nurses Guide to Understanding Laboratory and Diagnostic Tests. Philadelphia, PA: Lippincott Williams Wilkins.