The anergy panel is used to verify a patient’s ability to exhibit a delayed hypersensitivity response. It is commonly used in combination with the tuberculin purified protein derivative (PPD) skin test as a control. This serves to validate a negative PPD test.

A common antigen such as mumps, Candida, or trichophytin is injected intradermally at the same time as the
PPD tuberculin test. An individual with a normal immune response would produce a localized reaction to the injection within 48 to 72 hours. A lack of reaction suggests that the patient’s immune system is compromised, and therefore the results of a negative PPD test would be less conclusive. Such an individual should undergo a chest x-ray and sputum testing.

The angiotensin-converting enzyme (ACE) test is used to help diagnose and manage patients with sarcoidosis. Serum levels of ACE are increased in 85% of patients with active sarcoidosis. Normal levels may be found in dormant/inactive sarcoidosis. The ACE test is primarily used to evaluate the severity of the sarcoidosis and its response to therapy. ACE is found in pulmonary epithelial cells. It converts angiotensin I to angiotensin II, a potent vasoconstrictor. The ACE test is therefore sometimes used to evaluate special cases of hypertension. Clinical disorders that may increase ACE levels include active multiple sclerosis, histoplasmosis, amyloidosis, alcoholic cirrhosis, diabetes mellitus, Gaucher’s disease (a familial disorder of fat metabolism), Hodgkin’s disease, hyperthyroidism, leprosy, pulmonary embolism, idiopathic pulmonary fibrosis, scleroderma, and tuberculosis. ACE levels may be decreased in patients with sarcoidosis who are treated with prednisone. The ACE test is not done on patients less than 20 years old, because this age group normally has very high levels. Patients on ACE inhibitor medications will show low values. Smokers may have lower ACE levels than nonsmokers.

ANAs are immunoglobulin protein antibodies (IgG, IgM, IgA) that react against the nuclear material in leukocytes. They act as antibodies against DNA, RNA, and other nucleoproteins. The ANA test was developed to assess tissueantigen antibodies. It is often used to
diagnose SLE, an autoimmune collagen disease. Patients with autoimmune diseases have many abnormal antibodies. Two antinuclear antibodies, anti-DNA and antideoxyribose nucleoprotein, are almost always present in patients with SLE. The ANA test is quite sensitive in detecting SLE (˜95% of patients with SLE will show a positive ANA) but is not very specific, because many other disorders can cause a positive ANA. The ANA is therefore often used as a screening test for SLE. A negative ANA would suggest that it is unlikely that the patient has SLE. When a patient has a positive ANA, along with a positive LE (lupus erythematosus) prep, SLE would be strongly suspected.

Other disorders that can cause a positive ANA include systemic sclerosis, scleroderma, rheumatoid arthritis (RA), myasthenia gravis, leukemia, cirrhosis of the liver, ulcerative colitis, and infectious mononucleosis. Many drugs can also cause a positive ANA, including penicillin, tetracycline, acetazolamide, thiazides, and oral contraceptives.

Cardiolipin antibodies are the most common form of antiphospholipid antibodies. Antiphospholipid antibodies are the most common cause of thrombosis in nonelderly patients. Thrombosis may occur in response to transient APL elevations as well as in antiphospholipid syndrome. Transient increases in antiphospholipid levels occur in viral conditions including Epstein Barr, mumps, and measles. This test is also positive in some patients with SLE and places the patient at higher risk for “antiphospholipid syndrome” (venous or arterial thrombosis, thrombocytopenia, and recurrent spontaneous abortions).

The bleeding time (BT) is a test to evaluate the vascular and platelet factors associated with hemostasis. When vascular injury occurs, the first hemostatic response is a spastic contraction of the injured microvessels. Next, platelets adhere to the injured area. Failure of either process results in prolonged BT. Since this test is labor intensive and dependent on the operator’s skills, laboratories are beginning to use the platelet closure time test instead.

A small, standardized incision is made in the forearm, and the time required for the bleeding to stop is recorded. Because vessel constriction and platelet adherence are not affected by coagulation (intrinsic and extrinsic), defects in this system will not affect this test. It should be noted that the BT is only an indirect method of platelet function. A complete blood count (CBC) with platelet count should be performed to identify this directly. Prolonged BT with a normal platelet count indicates that a qualitative platelet disorder is present.

Renal function studies typically include the blood urea nitrogen (BUN) and creatinine tests. Both tests are included in blood chemistry panels. Renal involvement in diabetics and hypertensives can increase risk of retinopathy, making these tests of great interest to eye care practitioners. The BUN measures the amount of urea nitrogen found in the blood. Urea is formed in the liver as an end product of protein metabolism. It circulates in the blood and is excreted by the kidneys. The concentration of urea in the blood is directly related to how well the kidneys are excreting it. The BUN, therefore, is used as an indicator of liver and kidney function.

Most renal diseases decrease the kidney’s ability to excrete urea. The result is an increased BUN level. Other problems can also increase the BUN level. Dehydration from diarrhea, vomiting, or inadequate fluid intake can cause the BUN to elevate up to 50 mg/dL. The BUN should return to normal once the patient is rehydrated; if it does not, renal or prerenal failure should be suspected. Excessive protein intake causes the body to make large quantities of urea. The kidneys may become overloaded and be unable to excrete the excess urea. The BUN level will then rise. Gastrointestinal bleeding, diabetes, renal insufficiency because of shock and sepsis can all cause increased BUN levels. Many drugs can also elevate the BUN, including diuretics; antibiotics such as bacitracin, gentamicin, and neomycin; antihypertensive agents; sulfonamides; and salicylates. Older patients may also show an increased BUN, because the amount of nephrons tends to decrease with age. Because urea is formed in the liver, decreased BUN levels are seen in patients with severe liver damage. Low BUN levels may also indicate overhydration, malnutrition, or a low-protein diet. Pregnancy, which causes an increase in fluid volumes,
also reduces the BUN. Phenothiazines can also reduce the BUN.

There are several traditional and more advanced methods of testing for chlamydia. The methods are as follows:

Enzyme-linked immunosorbent assay. This common, rapid test detects substances (chlamydia antigens) that trigger the immune system to fight a chlamydia infection. EIA testing is done by taking a sample of secretions from the potentially affected area.

Direct fluorescent antibody (DFA) test. This is a common, inexpensive, rapid, and highly specific test that detects chlamydia antigens. DFA testing is done by taking a sample of secretions from the potentially affected area. This can be done as a slide test where the specimen is applied to a glass microscope slide, fixed, and sent to the lab. The lab applies monoclonal antibodies tagged with fluorescein. If the chlamydia antigen is present, fluorescent antigen-antibody complexes will form. DFA slide tests are available for many other organisms as well. This test is well suited for ocular specimens.

Nucleic acid amplification tests (NAATs). These tests detect the genetic material (DNA) of chlamydia bacteria. Testing can be done on either a urine specimen or a sample of secretions from the potentially affected area. Polymerase chain reaction (PCR) and ligase
chain reaction testing are examples of NAATs.

Nucleic acid hybridization tests (DNA probe testing). Probe testing also detects chlamydia DNA. Probe testing is very accurate and can be done by taking a sample of secretions from the potentially affected area. DNA probe testing is not as sensitive as NAATs. Gen-Probe by Pace is an example of a DNA probe test, which is approved for collection and testing of ocular specimens. The Gen-Probe Collection Kit from Pace comes in two different versions: one for cervical specimens with a larger swab and one for conjunctival and urethral specimens with a smaller swab. The collection kits contain an appropriate swab and chlamydial transport fluid. The same kit may be used for gonorrhea. The eye should be cleaned of any mucus and then the infected area swabbed and placed into the transport media. The specimen is then sent to the lab for processing. Other swab types and media cannot be substituted. This is an easy to collect, inexpensive, and sensitive test for chlamydia. The laboratory will typically supply you with the collection kits, but you can also order them independently.

Chlamydia culture. A culture provides the right environment for chlamydia bacteria to grow. This test is expensive and not commonly done. It requires high technical skills and results take 5 to 7 days. The chlamydia culture test is usually done when the number of bacteria is very low, when child sexual abuse is suspected, or when treatment for infection has failed. It is not recommended for ocular specimens.

Serum cholesterol levels are used in the diagnosis and management of atherosclerosis and coronary artery disease. They can also be used as an indicator of liver function because cholesterol is synthesized by the liver. Considering only the total cholesterol value can be misleading. Lipid (lipoprotein) profiles/panels that determine values for not only total cholesterol but also HDL, LDL, triglycerides (TGs), and risk factor for coronary disease are preferable.

Cholesterol is a blood lipid. It is found in red blood cells (RBCs), cell membranes, and muscle. Approximately 70% of cholesterol is in an esterified form (i.e., combined with fatty acids) and 30% is in the free form. Plasma cholesterol can be fractionated into high-density lipoprotein cholesterol (HDL-C), which makes up approximately 25% of the total cholesterol and normally ranges from 40 to 60 mg/dL, low-density lipoprotein cholesterol (LDL-C), and very-low-density lipoprotein cholesterol (VLDL-C). The body uses cholesterol to form bile salts for fat digestion and to form hormones made in the adrenal glands, testes, and ovaries. Hypercholesterolemia can lead to the formation of plaques in the coronary and carotid arteries. Elevated cholesterol levels (>250 mg/dL) may be seen in atherosclerosis, acute MI, hypothyroidism, biliary obstruction, uncontrolled diabetes mellitus, familial hypercholesterolemia, type II hyperlipoproteinemia, high-stress periods, high-cholesterol diet (animal fats), and pregnancy. Decreased cholesterol levels may be associated with hyperthyroidism, Cushing’s syndrome (adrenal hormone excess), anemias, acute infections, and malabsorption. Drugs that may decrease the serum cholesterol include the antibiotics neomycin and tetracycline, corticosteroids
such as cortisone, estrogens, glucagon, hypoglycemic agents, thyroxine, heparin, nicotinic acid, and aspirin. Drugs that may elevate the serum cholesterol include epinephrine, norepinephrine, steroids, androgens, oral contraceptives, sulfonamides, Thorazine, vitamins A and D, and aspirin.

The RBC count represents the number of circulating RBCs in 1 mm³ of blood. Reference values vary according to age and sex. A patient is said to be anemic if his or her RBC count is decreased by more than 10% of this expected reference value. There are many causes for low counts, including hemorrhage, anemias, chronic infections, blood dysplasias, chronic renal failure, dietary deficiencies, leukemia, overhydration, and pregnancy. An RBC count can also be greater than normal. Causes include
cardiovascular disease, high altitude, and polycythemia vera. Increased RBCs increase the blood viscosity and could put the patient at risk for thrombosis.

The hemoglobin test measures the total amount of Hb found in the blood. Hemoglobin is a pigment found in RBCs that carries oxygen. Most factors that affect the RBC count also affect the Hb concentration.

The Hb concentration, however, is more sensitive to fluid (plasma) volume changes. Abnormally high hemoglobin levels may result from dehydration. Overhydration may cause a low hemoglobin concentration. Clinical problems that may cause a decreased Hb level include anemias, cancers, sarcoidosis, and pregnancy. An elevated Hb may be caused by chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), polycythemia, and dehydration. Large elevations increase blood viscosity and therefore the risk of occlusion.

This is a measure of the percentage of RBCs in the total blood volume. The Hct is the volume (in milliliters) of RBCs found in 100 mL of blood, expressed as a percentage. If 45 mL of RBCs were found in 100 mL of blood, the Hct would be 45%. The Hct value should be about 3× the Hb value.

Factors that affect the RBC count and Hb concentration also affect the Hct. Clinical problems that may cause a decreased Hct include anemias, blood loss, leukemias, neoplasms, pregnancy, RA (especially juvenile), and vitamin deficiencies. An elevated Hct may be caused by dehydration, polycythemia, diabetic acidosis, and transient cerebral ischemia.

The MCV is a measure of the average volume or size of a single RBC. The MCV and the other RBC indices (MCH and MCHC) are used to help identify types of anemias. Reference values vary according to age and sex. If the MCV becomes abnormally large, the RBCs are termed macrocytic. Macrocytic RBCs are most frequently associated with megaloblastic anemias (vitamin B₁₂ or folic acid deficiency) or pernicious anemia. Macrocytic anemias are the type most likely to be associated with oculars signs. Microcytic RBCs (i.e., when the MCV value is abnormally small) are associated with iron deficiency anemia, malignancies, RA, sickle cell anemia, and thalassemia. If the MCV value is within the reference value range, the RBCs are termed normocytic.

The MCH is a measure of the average amount of Hb (by weight) within an RBC. The value is derived by dividing ten times the total Hb concentration by the number of RBCs:

MCH = Hb × 10/RBC count

The MCHC is a measure of the average concentration (weight per volume) or the percentage of Hb within a single RBC. It can be calculated from the MCV and MCH:

MCHC = MCH/MCV × 100 or

McHC = Hb × 100/HCr

It can also be derived by dividing the total Hb concentration times 100 by the Hct. If the MCHC value becomes abnormally low, RBCs are deficient in their concentration of Hb and are termed hypochromic. This condition is frequently seen with iron deficiency anemia and thalassemia. Elevated MCHC values do not occur because RBCs can only hold a physiologically limited amount of Hb.

The WBC count measures the total number of WBCs (leukocytes) in 1 mm³ of blood. It does not indicate the types of WBCs, only the number. WBCs are an important component of the body’s defense system and respond immediately to foreign invasion. The total WBC count has a wide normal range, but many diseases can significantly decrease or increase the count. An increase in WBCs is called leukocytosis. This
condition usually suggests infection or a leukemia. Stress, trauma, and tissue necrosis can also increase the total WBC count. A decrease in WBCs to less than reference values is called leukopenia. Diseases associated with this situation include viral infections, aplastic anemia, pernicious anemia, overwhelming infections, bone marrow failure, autoimmune diseases, and dietary deficiencies. Many drugs can also affect the WBC count. Drugs causing a decreased count include acetaminophen, barbiturates, chloramphenicol, penicillins, sulfonamides, Lasix, Valium, and Librium. Most chemotherapy agents significantly decrease values. Drugs that can cause an increased count include ampicillin, erythromycin, tetracycline, salicylates, and atropine (in children). The degree of increase or decrease in WBC values is directly proportional to the severity of the disease.

Normal, nonmedicated, nonpregnant adults:

The differential WBC count measures each type of leukocyte as a percentage of the total number of leukocytes. The leukocyte types observed on a peripheral blood smear are identified by their morphology. Neutrophils make up the largest percentage of leukocytes in adults. They are the most important leukocyte (because of their ability to use phagocytosis) in the body’s defense against infection and rapidly respond to acute infection, inflammatory disease, and tissue trauma. Eosinophils increase during allergic reactions, parasite infestation, and active sarcoidosis. Basophils prevent blood clotting during an inflammation. They contain granules of heparin and histamine. Lymphocytes make up the second largest group of leukocytes. They are seen to increase in conditions such as chronic bacterial infection, viral infection, infectious mononucleosis, lymphocytic leukemia, and multiple myeloma. Their numbers decrease as a result of immune deficiency diseases, steroid therapy, excess hormone production, or sepsis. Monocytes act as a second line of defense against infection. They respond more slowly than neutrophils to acute infection and inflammation, but once in action, they operate as powerful macrophages that continue into the chronic phase, ingesting dead tissue and debris and clearing the tissue for healing. Diseases in which monocytes increase include collagen diseases, RA, sickle cell anemia, viral diseases, herpes zoster, tuberculosis, toxoplasmosis, and cancers. The elevation, then, of any one type of leukocyte may serve as an important clue in the diagnosis of disease.

The computerized tomography (CT) scan can be used to detect diseases of the brain or orbit. The CT scanner produces a narrow x-ray beam that can examine the body from many different angles. A CT scan of the brain consists of a sequence of tomographic x-ray films taken of the brain tissue at successive layers. The films are subjected to a computerized analysis that builds up the shots into a three-dimensional (3D) picture. The CT x-ray image produced is a view of the head as if one were looking down through its top. Each type of tissue has its own density, and each permits the x-ray beam to penetrate only so far. An attached computer calculates the amount of x-ray penetration of each tissue. It displays this as varying shades of gray. The x-ray image appears on a television screen and is photographed. The denser the tissue, the lighter it appears in the image. The densest tissue appears white and less-dense tissue appears in progressively darker shades of gray. The result is an actual anatomic picture of a coronal section of the brain. The CT scan can be performed with or without iodine contrast dye. The iodine in the contrast dye causes a greater tissue absorption. This is referred to as contrast enhancement. A small tumor may not be observed if contrast enhancement is not used.

CT scans can be used to detect intracranial neoplasms, cerebral aneurysms, intracranial hemorrhages or hematomas, cerebral infarctions, cortical atrophy, arteriovenous malformations, or ventricular enlargement or displacement. CT scans can be repeated to monitor the progress of a disease or to monitor the effects of treatment. One advantage of the CT is that it has eliminated the need for more invasive procedures such as cerebral arteriography and pneumoencephalography.

The serum creatinine test and BUN are the tests most commonly used to assess kidney function. Both are included in standard chemistry panels. Creatinine is a by-product of muscle catabolism. It is derived from creatine phosphate, which is used in skeletal muscle contraction. The amount of creatinine produced daily is proportional to the amount of muscle mass. Creatinine circulates in the blood and is excreted by the kidneys. The concentration of creatinine in the blood is directly related to how well the kidneys are functioning. The serum creatinine level, then, can be used as an indicator of kidney function. It is considered to be a more specific and sensitive indicator of renal disease than the BUN, but the two tests are generally considered together. It is not influenced by diet or fluid intake and rises more slowly than the BUN. A small rise in the BUN may indicate dehydration, GI bleeding, or malnutrition; a serum creatinine of 2.5 mg/dL could indicate renal disease. When the BUN level rises but serum creatinine remains normal, dehydration is suspected. When both rise, the patient should be assessed for kidney disease. Clinical problems that can cause the serum creatinine level to rise include acute and chronic renal failure, hypertension, diabetic nephropathy, cancer, SLE, and a diet high in creatinine (lots of beef, poultry, and fish). Drugs that can elevate serum creatinine include antibiotics such as gentamicin and cephalosporin, barbiturates, and ascorbic acid. High intake of glucose or protein can also elevate serum creatinine. A decreased serum creatinine may be seen during pregnancy.

or

The ESR test is used to detect and monitor response to treatment of inflammatory conditions, infections, neoplasms, and necrotic processes. It measures the rate at which the RBCs in a sample of anticoagulated blood settle at the bottom of a narrow-bore tube in a 1-h period. The ESR is a nonspecific test and is not diagnostic for any specific disease or injury. The test can detect inflammatory
processes but can also be increased by acute and chronic infections, rheumatoid collagen diseases, neoplasms, pneumonia, syphilis, tissue necrosis, pregnancy, and general physiologic stress. All these conditions can cause an increase in the amount of protein (mainly fibrinogen and globulins) in the plasma. As a result, the repellent forces between adjacent RBCs begin to break down, and RBCs tend to stack on top of one another (rouleaux), increasing their weight and causing them to sediment faster than single cells. The ESR is therefore increased.

Decreased ESR values can also occur. Causes include CHF, polycythemia vera, sickle cell anemia, and hypofibrinogenemia. Some clinicians think the ESR is not that useful because it is so nonspecific and because it is affected by so many physiologic factors, it is best to order a C-reactive protein (CRP) test along with the ESR. CRP tends to increase more rapidly during an acute inflammatory process and return more quickly to normal than an ESR. The ESR, however, is a fairly reliable indicator for following the course of a disease. It is, therefore, mainly used to monitor the effects of therapy. Generally, the ESR will increase if a disease worsens and decrease as the disease improves. The ESR is also sometimes used to help with a differential diagnosis (e.g., RA versus osteoarthritis; or, in the case of a patient with chest pain, acute MI, which would show an increased ESR, versus angina pectoris in which the ESR would remain normal). One of the most important roles for the ESR in eye care is in the diagnosis and management of giant cell arteritis. Both CRP and ESR should be ordered in these patients. Both are indicators of inflammation. In the majority of affected patients, both tests will be significantly raised. Usually, the higher the value, the more active the disease is. If both tests are normal, it is highly unlikely that the patient has temporal arteritis, and imaging for other causes of vision loss should be performed.

Diabetes: greater than 126 FPG or 2-H OGTT ≥ 200 mg/dL. Screening with self monitoring devices: Although performed on capillary blood, which has slightly lower glucose values, most self-monitoring blood glucose instruments incorporate a compensation formula reporting the value as if it were plasma. Therefore, the same normal/abnormal ranges may be used for these devices. Refer for a physical examination and further testing if screening values are in either the diabetic or impaired range.

In most cases, the test of choice for detecting and diagnosing diabetes is the FPG. It is less expensive, less invasive, and more readily available than the oral glucose tolerance test (OGTT). Because most diabetics have the disease for 4 to 7 years prior to diagnosis and because diabetes is the leading cause of new blindness in adults aged of 20 to 74 years, early detection is crucial. Glucose is derived from dietary carbohydrates. It is stored in the liver and in skeletal muscle in the form of glycogen. Blood glucose levels are controlled by two hormones, insulin and glucagon, both produced by the pancreas. Insulin is necessary in order for glucose to enter cells. Glucagon helps the liver convert glycogen back into glucose.

An increased blood glucose level (hyperglycemia) occurs when there is an insufficiency of insulin. This condition indicates diabetes mellitus. However, there are other possible causes of an elevated blood sugar, including adrenal gland hyperfunction (Cushing’s syndrome), an acute stress response, acute MI, infections, renal failure, hyperthyroidism, and drugs such as diuretics and corticosteroids. For a diagnosis of diabetes, the patients must have abnormal tests on two different occasions. Tests could be random (casual glucose) with systemic symptoms, FPG, and/or 2-H OGTT.

Decreased blood glucose (hypoglycemia) also has many causes including hypothyroidism, Addison’s disease, cancer, extensive liver disease, malnutrition, and strenuous exercise. Additionally, there are many otherwise healthy people who tend to be consistently mildly hypoglycemic for no apparent pathological reason. This is generally managed by consuming more frequent smaller meals and nonsugary snacks throughout the day.

Adults:

Older adults:

This is a blood glucose test performed 2 hours after a meal.

The World Health Organization (WHO) recommends the GTT as the preferred way to diagnose diabetes. However, the American Diabetes Association (ADA) no longer recommends the glucose tolerance test (GTT) as the test of choice for diagnosis of most diabetes due to cost, invasiveness, and time required. ADA does recommend that it be performed (using the WHO procedure of 75 g glucose load) when the diagnosis is uncertain, for prediabetics, and in some cases of gestational diabetes. The GTT or OGTT measures a patient’s ability to handle a standard oral glucose load. Blood and urine samples are collected at specific times (before glucose administration, 30 minutes after, 1 hour after, 2 hours after, 3 hours after, and sometimes 4 hours after) and checked for their glucose levels. In most cases, the procedure will be stopped after collection of the

2 or 3 hour specimens. Normal patients handle the glucose dose easily and show only a minimal, transient rise in their blood glucose levels within 1 hour, and there is no glucose spillover into their urine. Diabetics are deficient in insulin and therefore have difficulty tolerating the standard glucose load. Their blood glucose levels will increase significantly between 1 and 5 hours, and glucose will usually be detected in their urine.

The GTT is contraindicated if the fasting blood sugar is over 200 mg/dL or if the patient has a serious concurrent illness, endocrine disorder, or infection (because a glucose intolerance will probably be observed even if the patient is not diabetic).

The peak glucose level for an oral GTT is usually observed within 30 minutes to 1 hour after ingestion of the standard dose. If the patient is normal, blood sugar should return to fasting level in 3 hours. Patients older than age 60 often have a blood glucose level 10 to 30 mg/dL higher than the “normal range.”

There are other causes of glucose intolerance besides diabetes. Elevated GTT values may be seen in patients
with hyperthyroidism, Cushing’s syndrome, hyperlipoproteinemia, cancer, duodenal ulcer, stress, infection, acute MI, and alcoholism. Elevations may also be seen in pregnant or obese patients. Certain drugs can also lead to increased GTT values, including corticosteroids, thiazide diuretics, salicylates, and oral contraceptives. Decreased GTT levels (<70 mg/dL at 3 hours) can also occur. Causes include hyperinsulinism, adrenal gland insufficiency, protein malnutrition, and malabsorption.

The FTA-ABS test is used to determine whether a patient has or has not had systemic syphilis. It is the most sensitive and specific test for diagnosing any stage of the disease and is the test of choice
for confirming a diagnosis. Once the test shows positive, it tends to remain positive indefinitely (even after treatment) in 95% of patients. Therefore, this test cannot be used to establish the activity of syphilis, how recently it was incurred, or how effective any treatment has been.

The FTA-ABS is usually ordered in combination with a rapid plasma reagin (RPR) or VDRL test to determine if the disease is active. If a patient has a positive FTA-ABS but shows a nonreactive RPR or VDRL, this indicates that the patient was exposed to Treponema pallidum (the causative agent for syphilis) or had syphilis sometime in the past but does not currently have the active disease. A positive FTA-ABS and a positive RPR or VDRL suggest that the patient has active syphilis. A negative FTA-ABS and a positive RPR or VDRL suggest a biological false-positive RPR meaning that the patient may have one of the many other conditions that result in a positive VDRL such as antiphospholipid antibody syndrome, mumps, measles, and other viral conditions. Since antiphospholipid antibodies may take several weeks to receive results, a positive VDRL could be an early clue of the reason for occlusion if it is known that the patient does not have syphilis.

False-positive FTA-ABS tests occur in about 1% to 2% of normals and may also occur in patients with collagen disease (e.g., SLE), but stained preparations from patients with SLE usually show an atypical beaded appearance not usually seen with syphilis.

Two newer tests for syphilis are the microhemagglutination assay for antibodies to T. pallidum (MHA-TP) and the hemagglutination treponemal test for syphilis. Both tests compare well with the FTA-ABS in terms of sensitivity and specificity (although the MHA-TP is less sensitive in primary syphilis). Their interpretation and use are also similar to that of the FTA-ABS.

The major histocompatibility locus antigens (HLAs) are extremely important in tissue recognition. Genes that regulate the HLAs are located on chromosome 6 at the HLA region. This region is composed of four closely linked genetic loci: HLA-A, HLAB, HLA-C, and HLA-D. Each person possesses two genes (one maternal gene and one paternal gene) at each of the four loci; this is because both mother and father contribute a complete haplotype of their HLA genes to each child. These eight genes together make up a person’s complete HLA phenotype. Antigens are named by giving them a letter representing their locus and a number that is unique for each antigen.

There are many HLAs, but the one with the most clinical significance is HLA-B27. Approximately 5% to 8% of normal white patients and a smaller percentage of normal black patients possess the HLA-B27 antigen. In whites, HLA-B27 is found in more than 90% of the patients with ankylosing spondylitis, 75% to 85% of patients with Reiter’s syndrome, 60% or fewer in those with psoriatic arthritis, and 20% to 50% of patients with acute uveitis regardless of the cause. In blacks with the same diseases, HLA-B27 is found to be about one-half as prevalent. HLA-B27 has also been associated with inflammatory bowel disease. The HLA-B27 antigen, then, can be used to help detect and diagnose some of these diseases, especially ankylosing spondylitis and Reiter’s syndrome.

Elevated homocysteine is associated with an increased risk of heart attack and stroke. It has also been associated with an increased risk of retinal vein occlusion.

Homocysteine is an amino acid that is produced as a by-product of meat consumption. Normally, it is converted to methionine and cysteine with the help of folic acid, B₁₂, and B₆. A shortage of these compounds can contribute to elevated levels of homocysteine. Elevated homocysteine levels have been associated with an increased risk of atherosclerotic vessel disease. Treatment includes folic acid and B vitamin supplementation.

The INR is a system established by the WHO and the International Committee on Thrombosis and Hemostasis for reporting the results of blood coagulation tests. All results are standardized using the international sensitivity index for the particular thromboplastin reagent and instrument combination utilized to perform the test. It is a
standardized version of the prothrombin time or PT test.

For example, a person taking the anticoagulant warfarin might optimally maintain a prothrombin time (PT) of 2 to 3 INR. No matter what laboratory checks the test time, the result should be the same even if different thromboplastins and instruments are used. This international standardization permits the patient on warfarin to travel and still obtain comparable test results.

Serum lipid levels are used to help diagnose and manage atherosclerotic disease. When lipids are transported in the blood, they are combined with proteins and called lipoproteins. There are two major classes of lipoprotein: HDL and LDL. LDLs have a strong association with atherosclerosis and coronary artery disease. HDLs are known as the “good” lipoproteins. They are associated with a decreased risk of coronary artery disease as they transport LDL away from the blood vessels and back to the liver for excretion from the body. Many doctors consider the HDL and total cholesterol/HDL ratio more important than the total cholesterol and/or LDL values. When there are increased levels of lipoproteins in the blood, the condition is called hyperlipidemia or hyperlipoproteinemia. There are six types of hyperlipoproteinemia, classified according to the major lipoprotein elevation and the major lipid elevation (Table 2-4). Types II and IV are the most common and most prevalent in atherosclerosis and coronary artery disease.

Clinical problems associated with increased lipid levels include type II hyperlipoproteinemia, hypothyroidism, diabetes, and a high-saturated fat diet. Decreased lipid levels may be associated with COPD and β-lipoproteinemia.