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Many patients seek dental care when they are recovering from serious illnesses; others have chronic conditions and take many medications. When medically evaluating patients, dental healthcare providers should employ four general concepts before providing dental care: Will the patient be able to survive the physiologic stress of the procedure? Will the patient have adequate hemostasis? Is there any increased susceptibility to infection? Will drug actions and interactions cause any complications?
Some of these questions can be answered by reviewing clinical laboratory test results. As with many other areas of healthcare, the use of laboratory testing has expanded greatly over the past decade, due largely to the development of automated testing devices and computerized reporting. These results about a patient's condition can provide valuable information for diagnosis and management of orofacial conditions, guidance on assessing the patient's ability to tolerate the proposed dental treatment, and a prognosis based on a particular treatment. The use of clinical laboratory tests (blood and other body specimens) in the general practice of dentistry is often limited because of a lack of education and training. This three-part series of articles describes the use of commonly available laboratory test results and provides general guidelines for evaluating a patient; however, this information should not be used in lieu of appropriate medical consultations and referrals. This particular article describes the use of the complete blood count and other hematology studies in dental care of patients.
Several important points about acquiring laboratory results should be noted. A patient with complex medical problems will likely receive routine tests ordered by the physician to monitor disease status, organ function, or metabolic reaction to medications. The most recent results should be readily available through the physician's office. When these are not accessible or if the dentist observes a sign of poor disease control, the physician should be consulted so that the physician can order the appropriate test(s). Occasionally, the dentist can specifically order a laboratory test. However, this implies a previous relationship with a testing laboratory and the understanding of medical diagnosis and procedure codes, which are necessary to include with the laboratory test in order to bill the patient's medical insurance company.
The typical laboratory report will include the patient's demographic data; date and time that the specimen was collected; and the ordering physician's name. The specific results will be accompanied by the laboratory's normal test range, which may vary between laboratories. Abnormal results are often indicated with H (high) or L (low) or may be printed in bold or color. Some reports will also include historical data, eg, the viral load results for a few years in a patient with human immunodeficiency virus (HIV), with comments regarding the degrees of change. While these indicators help, treatment decisions should never be made solely on these results.
Hematology: the Complete Blood Count
Routine hematology refers to a series of tests relating to the formed elements of the blood, including white blood cells (WBCs), red blood cells (RBCs), platelets, and red blood cell indices often referred to as the complete blood count (CBC). The CBC is one of the most commonly ordered blood tests in medicine and the preoperative assessment of patients.1-3 Many patients have baseline CBC tests to help determine general health status, and occasionally these tests may be used to evaluate specific components for dental care. These values are generally determined by special automated machines that rapidly analyze the different components of blood. The test tube containing the patient's blood sample is placed into the analyzer, which takes a microliter-sized amount of the blood into the actual testing area. For certain tests, electrical resistance is measured cell by cell, and the results are calculated to show the CBC with a differential by subset of cells. Other tests are completed by using a computer-assisted examination of a smear of the blood on a microscope slide, such as the measurement of the size of RBCs. If a patient has symptoms, such as fatigue or weakness, or an infection, inflammation, bruising, or bleeding, then the CBC findings may help diagnose the underlying cause. Significant increases in WBCs may help confirm the presence of a fulminant orofacial infection and suggest the need for antibiotics and/or hospitalization.
Decreases in RBC counts can be further evaluated by changes in the size or shape of the RBCs to help determine if the cause might be decreased production, increased loss, or increased destruction.4 For example, in macrocytic anemia, the RBCs are larger than normal; this may be due to nutritional deficiencies of vitamin B12 or folate that alter the development of the RBC. A low or extremely high platelet count may confirm the cause of excessive bleeding or clotting and can also be associated with bone marrow diseases, such as www.labtestsonline.org/understanding/conditions/leukemia.html.
Many conditions can result in fluctuations in the cell populations. Some of these conditions may require deferral of dental treatment, and the dental healthcare provider must understand the importance of these tests in developing a treatment plan and instituting modifications to care.1,2 Some diseases (eg, cancer) and chemotherapy can affect bone marrow production of cells, increasing the production of one cell at the expense of others, or decreasing overall cell production and leading to poor healing, excessive bleeding, and an increased risk of infection. Certain medications can decrease WBC counts while some vitamin and mineral deficiencies can cause anemia and oral symptoms. An evaluation of serial CBC results can reveal the course of these conditions and drug treatments, and, therefore, the timing of elective dental treatment can be influenced by the long-term course of these diseases rather than the current laboratory values. For example, when a patient is being treated with a medication that suppresses WBC production (such as antineoplastic agents), the patient is at a greater risk for postoperative infection, and dental treatment should be deferred until the WBC result is back to normal.
Extensions of hematologic tests include specific aspects about the RBCs, such as maturation and shape, and associated vitamins and minerals that may impact RBC formation and maturation (Table 1).
Erythrocyte/Red Blood Cell Count
The RBC count is the number of red blood cells per cubic millimeter of blood. Normal range varies slightly between laboratories but is generally 4.2 million cells/mm3 to 6.1 million cells/mm3. The RBC count is also called the erythrocyte count. Erythropoietin, secreted mainly by the kidneys, stimulates the bone marrow to produce RBCs. In kidney disease, erythropoietin production may be reduced, leading to anemia. Tissue hypoxia can lead to increased erythropoietin secretion and subsequently greater levels of RBCs. Physiologic increases in RBCs (erythrocytosis) occur with a move to higher altitude or with increased physical training.5-7 The response to decreased oxygen at higher altitudes results in a compensatory production of RBCs from the marrow, while physical activity creates greater muscle mass and, therefore, greater oxygen demand. These physiologic changes are different than pathologic elevations in RBCs seen in primary and secondary polycythemia.6 Polycythemia vera, a rare marrow disorder, is an abnormal increase in the number of RBCs, WBCs, and platelets produced by the bone marrow.7 Although polycythemia does not have any specific oral manifestations, most patients are at an increased risk of thrombotic events and may be treated with anticoagulants or antiplatelet medications.6 Major bleeding is rare in patients with untreated polycythemia vera, but some patients also have a qualitative platelet disorder that may increase the risk for bleeding after invasive routine dental care.6 Patients with polycythemia may experience orthopnea in the dental chair, dizziness, headache, red facial coloring, and dyspnea.6,7 Rarely, there is an increased risk of patients developing a hematologic malignancy such as leukemia.5-7
Anemia is a commonly used, nonspecific term that suggests a decreased RBC count, decreased hemoglobin (Hgb) levels of RBCs, or both. By using other RBC indices, ie, mean corpuscular volume or mean corpuscular hemoglobin concentration (see section below), the pathogenesis of the anemia can be classified.8,9
Hemoglobin and Hematocrit
Reported as the amount of Hgb in a volume of blood, hemoglobin is the protein molecule in red blood cells that carries oxygen and gives blood its color. Hemoglobin is composed of four heme groups and four globin protein subunits that form a tetrahedral structure. The heme groups are where the iron ions exist and where the oxygen atoms are held. The normal range for hemoglobin differs between the sexes and is approximately 13 g/dL to 18 g/dL for men and 12 g/dL to 16 g/dL for women. Because normal erythrocytes contain the ideal concentration of Hgb, any increase in Hgb must be evaluated in relation to erythrocyte number and size. Elevated Hgb levels are seen in polycythemia.7 Lowered levels of Hgb are observed in any condition known to cause a decreased RBC count. Some of the more common conditions encountered in clinical dental practice include blood loss (eg, menses) or gastrointestinal bleeding, hemolytic anemia, and any type of bone marrow suppression. Also, a number of conditions result in abnormal types of Hgb, which tend to be fragile and easily destroyed in the vascular system. They include sickle cell anemia, glucose-6-phosphate dehydrogenase deficiency, and thalassemias.10-16
Hgb values are used with hematocrit (Hct) to assess erythropoiesis. If each erythrocyte has a normal concentration of Hgb, the Hct is roughly three times the Hgb level. Hgb and Hct are necessary parts of the assessment for anemias and in patients with burning mouth disorders and aphthous stomatitis. Both glossitis and dysphagia are classic symptoms of iron deficiency anemia.10 Hct, or packed cell volume, is a percentage of RBCs in plasma based on the assumption that the plasma volume is normal, and can vary with dehydration or other volume loss. Because the Hct is a proportion of the RBCs to overall fluid volume, there can be an increased Hct level without an increased RBC. Decreased Hct indicates anemia, such as that caused by iron deficiency or other nutritional deficiencies.17 Further testing is often necessary to determine the cause of the anemia. Other conditions that can result in a low Hct level include vitamin or mineral deficiencies, recent bleeding, cirrhosis, and malignancies.18-20 Like Hgb, the references ranges for Hct vary between men and women (men = 37% to 49%; women = 36% to 46%). Whole blood transfusions are generally not considered for otherwise healthy persons as long as the Hgb level is above 8 g/dL or the Hct is above 24%.
Red Blood Cell Indices and Red Blood Cell Distribution Width
Mean corpuscular volume (MCV) is a measurement of the average size of RBCs. The MCV is elevated when RBCs are larger than normal (macrocytic), eg, anemia caused by vitamin B12 or folate deficiency.21,22 When the MCV is decreased, RBCs are smaller than normal (microcytic) as is seen in iron deficiency anemia or thalassemia. Mean corpuscular hemoglobin (MCH) is the average amount of oxygen-carrying Hgb in a red blood cell. Macrocytic RBCs are large, so they tend to have a higher MCH, while microcytic red cells would have a lower value. Mean corpuscular hemoglobin concentration (MCHC) is the average concentration of hemoglobin in an erythrocyte. Decreased MCHC values (hypochromia) are seen when the hemoglobin is abnormally diluted in the red cells, such as in iron deficiency anemia and thalassemias. Increased MCHC values (hyperchromia) are observed when the hemoglobin is abnormally concentrated in the red cells, such as in burn patients and hereditary spherocytosis, a relatively rare congenital disorder.23 Red cell distribution width (RDW) is a calculation of the variation in the size (larger or smaller than normal) of RBCs. It is expressed as a percentage of abnormally sized RBCs, typically between 11% and 15%. In some anemias, such as pernicious, the amount of variation (anisocytosis) in RBC size and shape (poikilocytosis) causes an increase in RDW.
Bleeding disorders or bone marrow diseases, such as leukemia, require the dental healthcare provider to determine the number of platelets present and/or their ability to function correctly prior to invasive surgery. In an adult, a normal platelet count is approximately 150,000 to 450,000 per cubic millimeter (mm3)of blood. It has been reported that increased clinical bleeding is seen with counts below 50,000 platelets per mm3 of blood, and spontaneous bleeding is common if the platelet levels fall below 20,000 per mm3.24,25 Thrombocytopenia (low platelet count) is considered a life-threatening risk and may warrant immediate medical evaluation and platelet transfusions. In the author's opinion, invasive elective dental care should be deferred in cases with platelet counts below 50,000 per mm3.
Thrombocytopenia is commonly seen in patients who have a hematologic malignancy, such as leukemia. As the number of malignant cells increases in the bone marrow, normal bone marrow cells are crowded out, resulting in fewer platelet-producing cells.25 Thrombocytopenia also may be observed in some patients with long-term bleeding problems (eg, chronic bleeding stomach ulcers), HIV/AIDS, and gram-negative sepsis.25 Individuals with autoimmune disorders, such as lupus or idiopathic thrombocytopenia purpura (ITP), develop antibodies that attack and destroy platelets.24 Certain medications, including acetaminophen, heparin, quinidine, sulfa, digoxin, vancomycin, valium, and nitroglycerine, can induce thrombocytopenia.26 Patients receiving chemotherapy or radiation therapy may also have a decreased platelet count. As much as 6% to 10% of pregnant women may experience thrombocytopenia at term.27 Aspirin and nonsteroidal anti-inflammatory drugs are inhibitors of platelet function but do not affect quantity.
Platelet destruction may be observed in renal diseases due to decreased lifespan from uremic toxins in blood or destruction during hemodialysis. Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are also seen in renal failure and can result in fewer circulating platelets in the blood.24-26 Von Willebrand's disease, a common condition (affecting approximately 1% of the population) that causes easy bruising or bleeding, is often associated with platelet dysfunction. While the platelet counts may be normal, they have reduced ability to adhere and aggregate due to a decrease in von Willebrand's factor, a protein needed to initiate clotting.28 Many cases may not be diagnosed due to the mild nature of the disease and are only discovered when a patient needs minor surgery or tooth extraction.28
Increased platelet counts (thrombocytosis) may be seen in individuals who show no significant medical problems, while others may represent a myeloproliferative disorder of the marrow. Although they have an increased number of platelets, some patients have a tendency to bleed due to platelet dysfunction; while in others, the platelets function normally but because they are increased in number, tend to overaggregate, leading to thromboembolism or infarction.
Reticulocytes are anuclear, immature erythrocytes in the bloodstream. Once in the blood, these cells lose their reticulum and mature into erythrocytes. The reticulocyte count helps determine if the bone marrow is responding adequately to the body's need for RBCs and helps identify the cause and classify types of anemia. Normally, in about 1% to 2% of cases, an increase in the percentage of reticulocytes suggests an increased release of RBCs from the bone marrow into the bloodstream. This is a physiologic response in acute blood loss or seen in response to iron therapy for iron deficiency anemia.20 An increased reticulocyte count is a positive indication that the bone marrow is responding normally. A reticulocyte count may be ordered with a decreased labtestsonline.org/understanding/analytes/rbc/glance.html">RBC count and/or a decreased hemoglobin and hematocrit to evaluate bone marrow function. An increased reticulocyte percentage may indicate conditions such as hemorrhage, hemolytic anemia, and hemolysis of the newborn. Decreased reticulocyte percentages are commonly observed with iron deficiency anemia, folate deficiency, B12 deficiency, aplastic anemia, radiation therapy, or bone marrow failure due to chemotherapy or infection.18-20
Erythrocyte Sedimentation Rate
Erythrocyte sedimentation rate (ESR) is a nonspecific measure of inflammation. It helps gauge the rate of fall (sedimentation) of erythrocytes in a tube of blood. ESR results are reported as the number of millimeters of clear plasma present above the RBCs that have settled in the test tube after 1 hour, such as 15 mm/hour. The results vary by age and sex. Normally, red cells fall slowly, leaving little clear plasma. Increased blood levels of certain proteins (such as fibrinogen or immunoglobulin, which are elevated in inflammatory diseases) cause the red blood cells to fall more rapidly, increasing the ESR.21 Infections, including chronic periodontal disease, cancers, and autoimmune diseases are a few of the many types of processes that can lead to elevated ESR. The change in ESR may be used to evaluate the effectiveness of therapeutic medications.29
ESR is helpful in diagnosing two specific inflammatory diseases—temporal arteritis and polymyalgia rheumatica.29,30 Temporal arteritis is a granulomatous inflammation of the temporal artery that manifests as orofacial pain and is often misdiagnosed as temporomandibular disorders. Accurate and early management is vital because this disease can lead to blindness due to ischemic necrosis of the optic nerve.29 ESR has gained recent attention in the dental literature because of the growing evidence of an association between periodontal disease and cardiovascular disease and the role ESR and other acute phase reactants such as C-reactive protein play in the evaluation of the dental patient. Researchers are also investigating whether these tests can help predict adverse cardiovascular outcomes in patients who have chronic periodontal disease.29,30
Total White Blood Cell Count and Differential
There are five types of leukocytes (white blood cells [WBCs])—neutrophils, lymphocytes, monocytes, eosinophils, and basophils—each with different functions (Table 2). The WBC differential reveals whether these leukocytes are present in normal proportion to one another, one cell type is increased or decreased, or immature cells are present. The white blood cell differential is used to assess the body's ability to respond to and eliminate infection, possibly detect the severity of allergic and drug reactions, and evaluate the response to parasitic and other types of infection. The WBC differential is essential in evaluating the reaction to viral infections such as HIV/AIDS, and the response to chemotherapy and bone marrow or stem cell transplantation following myeloablative treatments.31,32 It can also identify various stages of hematologic malignancies.31
Because percentages of WBCs might be misleading in some patients, absolute values of the various types of WBCs can also be reported, such as the absolute neutrophil count (ANC), also known as the absolute granulocyte count (AGC). Absolute values are calculated by multiplying the number of WBCs by the percentage of each type of white cell and can aid in diagnosing illness and monitoring therapy. For invasive dental treatment, perioperative antibiotics are indicated in patients with ANC less than 1,000 cells/mm3 in order to minimize the risk of infection. When the ANC falls below 500 cells/mm3, intravenous antimicrobial therapy may be necessary to prevent sepsis resulting from invasive dental treatment.31,32
Lymphocyte counts can increase in cases of viral infection, leukemia, bone marrow cancer, or radiation therapy. Decreased lymphocyte levels can indicate diseases that affect the immune system, such as lupus; specific subsets of lymphocytes, the CD4 and CD8 cells, are used to assess the stages of HIV. Neutrophils can increase in response to bacterial infection or inflammatory disease. Severe elevations in neutrophils may be caused by various bone marrow disorders, such as chronic myelogenous leukemia. Decreased neutrophil levels may be the result of severe infection or other conditions, such as responses to various medications, particularly chemotherapy.31 Eosinophils can increase in response to allergic disorders, inflammation of the dermis, and parasitic infections. They can also increase in response to some infections or various bone marrow disorders. Infection can cause decreased levels of eosinophils. Basophil levels can rise in leukemia, chronic inflammation, hypersensitive reaction to food, or radiation therapy. Monocyte levels can increase in response to all kinds of infection, as well as inflammatory disorders. Monocyte counts are also increased in certain malignant disorders, including leukemia. Decreased monocyte levels can indicate bone marrow injury or failure and some forms of leukemia. Table 3 summarizes some causes of high and low WBCs.
Supplementary information gathered from history and examination by the oral healthcare provider is often necessary for treating dental patients. In addition to radiography, clinical laboratory evaluations may aid the clinician in diagnosing oral disease (eg, aphthous stomatitis, by ruling out other causes of oral ulcers such as anemia),33 determining the severity of infection (eg, facial cellulitis), or modifying the provision of dental care based on underlying disease and proposed dental treatments. An understanding of common laboratory testing is a vital tool in the armamentarium of the treatment of the growing numbers of medically complex and geriatric patients.
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About the Authors
Wendy S. Hupp, DMD
Assistant Professor of Oral Medicine
Department of General Dentistry and Oral Medicine
University of Louisville
School of Dentistry
F. John Firriolo, DDS, PhD
Professor and Director
Division of Oral Medicine
Department of General Dentistry and Oral Medicine
University of Louisville|
School of Dentistry
Scott S. De Rossi, DMD
Associate Professor of Oral Medicine
Chairman, Department of Oral Health and Diagnostic Sciences
Medical College of Georgia