Blood will tell - Pharmaceutical Representative

Lab tests are an important way for physicians to diagnose their patients. Learning why and when physicians order certain lab tests will help you understand some of the issues doctors face in their day-to-day practices. This two-part article will familiarize you with the laboratory tests that physicians and other prescribers commonly order. The clinical significance of each test will be described, and the medications that either treat the related pathologies or affect the test value itself will be mentioned.

Blood basics

The average adult has about five liters of blood. Sixty percent of this is liquid (called plasma), and 40% is cells, divided into red cells, various types of white cells and platelets.

The most commonly ordered blood test battery is the complete blood count (CBC). The tests included in the CBC are the red blood count (RBC), the white blood count (WBC), hemoglobin (Hb), hematocrit (Hct), various red blood cell indices and the platelet count. Physicians will order a CBC if they suspect one of many pathologies, but it is far more often ordered as a general health screening.

Before describing the components of the CBC and their interpretations, it is of interest to mention a study of physicians that was published in the American Journal of Clinical Pathology (vol. 118, no. 5). Physicians were asked how useful CBC results really are in their actual practices, and amazingly, only four of 11 tests within the CBC were described by the doctors surveyed as "frequently or always useful." Those were the Hb, Hct, platelet count and WBC tests. The hematocrit was described as useful by 98% of doctors surveyed, making it the most valued part of the CBC. This article will focus on these four parameters in addition to the red blood cell count, another extremely important component of the complete blood count.

When examining any blood test result, it is important to keep in mind that normal values vary based on many factors, such as age, race, sex of the patient, pregnancy and the particular laboratory performing the test, among many others. Because these values are readily available elsewhere, they will not be listed here.

Let's now look at the CBC components, the major pathologies with which they are associated and the pharmaceutical categories that play roles either in these pathologies or in the test results themselves.

Red blood cell count

Red blood cells, also called erythrocytes, carry oxygen from the lungs throughout the body and bring carbon dioxide from the body tissues back to the lungs, where it is exhaled. The RBC test measures the number of these cells in a cubic millimeter of blood.

Decreased RBCs occur in anemias, a large group of diseases in which red cells are too few in number due to their destruction, their loss due to bleeding, or their insufficient or defective production. Red blood cells are also found in decreased quantities in many malignant disorders such as Hodgkin's disease, leukemia and multiple myeloma. Chronic infection can also cause an abnormally low RBC result.

Increased red blood cell counts, also called erythrocytosis, can occur due to abnormally active production in the bone marrow or for secondary reasons outside the bone marrow, such as renal disease, pulmonary disease, dehydration and even exposure to high altitude, which causes the body to find a way to obtain sufficient oxygen.

As is apparent from the examples above, abnormalities in the RBC can serve as clues to a number of diverse pathologies involving one or several organ systems. Keeping this fact in mind, we can create a very abbreviated list of medications that may be indicated for certain patients with altered red blood cell counts. These medications include: antibiotics, oncologic agents, anticoagulants and vitamin K.

Hematocrit

The hematocrit is a measure of red blood cell mass. It is calculated by spinning blood in a centrifuge and then measuring the percentage (by height in the test tube) of the blood that consists of packed red blood cells (versus liquid, or plasma). Increases and decreases in hematocrit values generally mirror the values of the red blood cells, as might be expected.

An interesting disorder that causes increases in hematocrit, total red cells and often hemoglobin is polycythemia vera. This illness is caused by excessive production of red cells in the bone marrow for unknown reasons. The disease essentially results in thickening of the blood, which can lead to clotting that can cause visual problems, stroke and myocardial infarction. The treatment for this condition is phlebotomy, in which about a liter of blood per week is removed from the patient until the hematocrit drops to a normal level.

Hemoglobin

Hemoglobin is the oxygen-carrying component of the blood. It consists of heme, which contains iron and a red pigment called porphyrin (which makes blood red), and a protein called globin. Decreases in hemoglobin occur in many anemias, in autoimmune illnesses such as lupus and in hemorrhage. Hemoglobin increases in polycythemia vera, during congestive heart failure and in chronic obstructive pulmonary disease. The medications that affect hemoglobin generally mirror those that affect other red cell parameters.

Red cell indices that are part of the CBC but are generally thought of as less clinically useful than the above indices are the mean corpuscular volume (or MCV), the mean corpuscular hemoglobin concentration (or MCHC) and the mean corpuscular hemoglobin (or MCH).

White blood count

White blood cells (also called leukocytes) are important in maintaining the body's defense against infection. They engulf dangerous organisms by a process called phagocytosis and also help antibodies fight offending agents classified as antigens. There are two major categories of white blood counts. The first is granulocytes (neutrophils, basophils and eosinophils), which have granules in their cytoplasm and multi-lobed nuclei. Doctors often call these cells "polys" or "polymorphs" because of the multiple lobes in their nuclei. The second category consists of white cells with just one lobe in the nucleus and no granules (monocytes and lymphocytes).

There are many causes of decreased white counts (leukopenia). Although most bacterial infections increase total white count, very severe ones can cause a decrease; viral infections can also cause leukopenia. Diseases or external agents, particularly medications, can cause bone marrow suppression, which may lead to decreased white cell counts.

Illnesses that cause leukopenia also involve bone marrow suppression; these include pernicious anemia and some rare genetic syndromes. Pathologies that occupy space in bones, such as certain tumors, result in less total bone marrow and thus fewer white cells than normal.

Environmental substances, such as heavy metals, and radiation can also suppress the marrow and lower the white count. The following categories of medications make up a partial list of drugs that can contribute to leukopenia: analgesics, antibiotics, anticonvulsants, antihistamines, anti-inflammatories, antithyroids, barbiturates and diuretics.

Increases in white count (leukocytosis) occur in many clinical situations, but the increase is usually due to only one type of cell increasing in number. In infection, the type of infectious agent involved will cause an increase in the white blood cell best suited to eradicate that agent (see "The differential" below). One of the most serious pathologies that cause leukocytosis is leukemia. Other malignancies can also cause increases in white count, particularly bronchogenic carcinoma. Certain illnesses, such as pertussis and measles, can cause a high leukocytosis that resembles that of leukemia but is temporary. This is called a leukemoid reaction.

Medications that can cause an increase in white count include: ether and other anesthetic agents, quinine, epinephrine, and steroids, such as ACTH.

The differential

The CBC is usually ordered with a "differential" or "diff," which refers to the quantification of the different types of white blood cells. The major types of white blood cells have different roles in fighting disease. An increased value for a specific type of white blood cell implies increased activity against a particular type of pathogen:

* Neutrophils (the most prevalent white blood cells) generally function against bacterial infections.
* Eosinophils generally function against allergies and parasitic infections.
* Basophils generally function against parasitic infections.
* Lymphocytes generally function against viral infections.
* Monocytes generally function against severe infections.

Physicians often refer to a "shift to the left" or "bands" or "stabs" in regard to the differential when a patient is thought to have an infection, particularly a bacterial infection. These terms refer to the increased production of neutrophils, many of which are immature because they're forming quickly to fight the infection. The nuclei of these immature cells have not yet had a chance to form multiple nucleus lobes, so they look more like bands than true nuclei. "Shift to the left" means that the cells have not evolved (to the "right" of their evolutionary scale, so to speak) into mature neutrophils.

It is advisable for pharmaceutical representatives to review the package inserts of the products they promote (and those of the competition), paying particular attention to laboratory findings that may be affected by these products. Physicians will appreciate this information, particularly if they are challenged when attempting to interpret a perplexing laboratory result.

The next article on lab tests will deal with electrolytes, blood chemistries and other important common blood tests.

About the Author

Neil Berliner, M.D.