Blood Studies

Blood is the body fluid most frequently used for analytic purposes. Blood studies are used to assess a multitude of body processes and disorders. Common studies assess the quantity of red and white blood cells, and the levels of enzymes, lipids, clotting factors, and hormones. Most blood studies are performed for one of the following reasons:

1. To establish a diagnosis (e.g., high blood urea nitrogen [BUN] and creatinine levels are indicative of renal failure).

2. To rule out a clinical problem (e.g., hypokalemia is ruled out with a normal potassium level).

3. To monitor therapy (e.g., glucose levels are used to monitor treatment of diabetic patients, and partial thromboplastin time [PTT] values are used to regulate heparin therapy).

4. To establish a prognosis (e.g., declining CD4 counts reflect a poor clinical prognosis for the acquired immunodeficiency syndrome [AIDS] patient).

5. To screen for disease (e.g., prostate-specific antigen levels are used to detect prostate cancer).

6. To determine effective drug dosage and to prevent toxicity. (Peak and trough levels are drawn at designated time periods; see p. 21.)

Methods of Blood Collection

There are three general methods for obtaining blood: venous, arterial, and skin puncture. Blood collected from these sites differs in several important aspects. For example, arterial blood is oxygenated by the lungs and pumped from the heart to body organs and tissues. It is essentially uniform in its composition throughout the body. Venous blood composition varies depending on the metabolic activity of the organ or tissue being perfused. Venous blood is oxygen-deficient in comparison to arterial blood. Variations between arterial and venous blood are often seen in measurements of pH, CO₂ concentration, and glucose, lactic acid, and ammonia levels. On the other hand, blood obtained by skin puncture is a mixture of arterial and venous blood. Skin puncture blood also includes intracellular and interstitial fluid. By far the most common access for blood withdrawal is venous puncture.

Venous Puncture

Background Information

The ease of obtaining venous blood makes this the primary source of blood collection. It is relatively free of any complications. Venipuncture is usually obtained by drawing a specimen of blood from a superficial vein (Figure 2-1). The site most often used is the antecubital fossa of the arm because there are several large superficial veins at that location. The basilic, cephalic, and median cubital veins are the most commonly used sites. Veins of the wrist or hand can also be used. When venous puncture cannot be performed on the upper extremities, the femoral vein is the most easily accessible for puncture.

Figure 2-1 Venipuncture.

Collection Tubes

Venipuncture is usually accomplished using needles attached to glass tubes under specified vacuum. A needle and a syringe can also be used to collect the blood sample and then to inject it into the appropriate tube. Tubes come in various sizes (2, 3, 5, 7, 10, and 15 mL). The rubber stoppers are color-coded to distinguish whether the tube is a plain tube (e.g., no preservatives or anticoagulants added), whether the tube contains a specific anticoagulant (such as heparin, oxalate, citrate, or ethylenediamine tetraacetic acid salts [EDTA]), or whether the tube is chemically clean (e.g., iron determination). Depending on the tests needed, the analysis is performed on whole blood, serum, or plasma. A centrifuge is used to separate the blood components and to obtain either serum or plasma. Whole blood collected without anticoagulant clots, and serum can be separated out for testing. Whole blood collected with an anticoagulant prevents clotting, and plasma can be tested. Plasma contains fibrinogen, which is missing from serum.

The selection of the color-coded tube is based on the requirements of the test. Charts are available from the laboratory that indicate the type of tube needed for a particular blood test. Colors and amount of blood required may vary according to the laboratory. A representative chart is shown in Table 2-1.

TABLE 2-1

Blood Studies

1. Blood culture tubes first (to maintain sterility)

2. Nonadditive tubes (e.g., red top)

3. Coagulation tubes (e.g., blue top)

4. Heparin tubes (e.g., green top)

5. EDTA-K3 tubes (e.g., lavender top)

6. Oxalate-fluoride tubes (e.g., gray top)

Technique

Arterial Puncture

Background Information

Arterial blood is used to measure oxygen, CO₂, and pH. These are often referred to as arterial blood gases (ABGs) and are described on p. 109. If a patient will require frequent sampling, an indwelling arterial catheter is usually placed. Arterial puncture is used for single or infrequent sampling.

Arterial punctures are more difficult to perform than venipuncture. They also cause a significant amount of patient discomfort. The brachial and radial arteries are the arteries most often used for arterial puncture. The femoral artery is usually avoided because bleeding occurs more often after the procedure and may not be noted because it is hidden by bed covers. Large amounts of blood could be lost before the problem is detected.

Technique

Before

Explain the procedure to the patient. Inform the patient why this blood test is necessary. Tell the patient that the test causes more discomfort than a venipuncture.

• Notify the laboratory before drawing arterial blood samples so the necessary equipment can be calibrated before the blood sample arrives.

• Perform the Allen test to assess collateral circulation before performing the arterial puncture on the radial artery. To perform the Allen test, make the patient's hand blanch by obliterating both the radial and ulnar pulses. Then release the pressure over the ulnar artery only. If flow through the ulnar artery is good, flushing will be observed immediately. The Allen test is then positive and the radial artery can be used for venipuncture. If the Allen test is negative (no flushing), repeat it on the other arm. If the results are negative in both arms, choose another artery for puncture. The Allen test is important because it ensures collateral circulation to the hand if thrombosis of the radial artery occurs after the puncture.

• Assemble appropriate equipment and specimen container for the specimen. Put on protective gloves.

During

• Cleanse the arterial site with 70% isopropyl alcohol. Allow the site to dry.

• Attach a 20-gauge needle to a syringe containing approximately 0.2 mL of heparin. Insert the needle at a 45- to 60-degree angle into the skin over the palpable artery (Figure 2-4).

Figure 2-4 Drawing arterial blood. Note that the needle is at a 45-degree angle.

• After drawing approximately 3 to 5 mL of blood, remove the needle and apply pressure to the arterial site for 3 to 5 minutes. Expel any air bubbles in the syringe and activate the protective cover.

• Cap the syringe and gently rotate to mix the blood and the heparin.

After

• Indicate on the laboratory slip if the patient is receiving any oxygen therapy or is attached to a ventilator.

• Place the arterial blood on ice and immediately take it to the chemistry laboratory for analysis.

• If the patient has an abnormal clotting time or is taking anticoagulants, apply pressure for approximately 15 minutes. A pressure dressing is usually applied.

Potential Complications

• Arterial thrombosis. Thrombosis can result and impair arterial circulation. This can result in ischemia or necrosis of tissue on the extremity.

• Hematoma formation. Pressure must be applied to the arterial puncture site for at least 3 to 5 minutes to prevent hematoma formation (longer if the patient is anticoagulated). If a hematoma results, warm compresses will enhance absorption of the blood.

• Bleeding. The site must be carefully assessed for bleeding. An arterial puncture can cause rapid bleeding. This is especially important if the patient has an abnormal clotting time or is taking anticoagulants.

Skin Puncture

Background Information

Skin puncture (sometimes called capillary puncture) is the method of choice for obtaining blood from pediatric patients, especially infants, because large amounts of blood required for repeated venipuncture could result in anemia. However, skin punctures are also used in adult patients.

Common puncture sites include the fingertips, earlobes, and heel surfaces. The fingertips are often used in adults and small children. The heel is the most commonly used site for infants. The earlobe can be used to obtain blood in adults and older pediatric patients. The earlobe can also be used to obtain arterialized capillary blood as a possible substitute for arterial blood in determining the pH, PCO₂, and PO₂.

With changes in health care economics and delivery, the use of skin punctures will probably increase. Blood monitoring will be increasingly performed in outpatient settings. Clinical laboratory tests will be performed more frequently at the bedside using a skin puncture.

Technique

Before

Identify the patient using two separate identifiers. Explain the procedure to the patient and/or family. Assemble all supplies. Put on gloves.

• Select an appropriate puncture site. For infants, the lateral or medial heel surface is commonly used. For older infants, children, or adults, the lateral aspect of the second, third, or fourth fingertip may be used to avoid the central tip of the fingers where the nerve supply is more dense.

During

• Warm the puncture site with a warm, moist towel to increase blood flow.

• Cleanse the puncture site with 70% isopropyl alcohol. Allow the site to dry.

• Make the puncture with a sterile lancet or skin puncture device.

• Discard the first drop of blood by wiping it away with a sterile pad.

• Do not milk the site, as this may hemolyze the specimen and introduce excess tissue fluid. Also avoid using excess pressure on the fingers during blood collection. This may cause hemolysis of the sample.

• Collect the specimen in capillary tubes or on special filter papers.

• If using capillary tubes, seal the capillary tubes by inserting clay into the end of the micropipette.

After

• Initial the blood label and record the time and date of blood collection. Indicate that the blood was collected by skin puncture.

• Arrange for prompt transportation of the blood specimen to the laboratory.

Potential Complications

• Infection. Assess the skin puncture site for redness, swelling, pain, or tenderness. Although this is a serious complication, the incidence is very low.

• Hematoma and bruising. Check the skin puncture site for discoloration, bruising, or swelling. Look for bleeding onto the skin. Avoid frequent skin punctures or excessive squeezing of the tissue during blood collection to prevent this problem.

Timing of Blood Collection

Although many blood specimens can be obtained randomly, some must be drawn at specific times. For example, lipoproteins (see p. 342) should be drawn after a 12- to 14-hour fast (except for water), because food can alter lipoprotein values. Because glucose levels are related to food intake, fasting blood glucose specimens require an 8-hour fast. Glucose tolerance tests (see p. 261) require a fasting blood glucose level and a glucose level drawn at 30 minutes, 1 hour, 2 hours, 3 hours, and sometimes 4 hours after glucose administration.

Specimens for therapeutic drug monitoring (see p. 211) must be obtained at specific times determined by the method of drug delivery (e.g., IV or oral), dosage interval, absorption characteristics of the drug, and half-life of the drug. Drug monitoring is especially important in patients taking medications (such as antiarrhythmics, bronchodilators, antibiotics, anticonvulsants, and cardiotonics), because the margin of safety between therapeutic and toxic levels may be narrow. Blood levels can be taken at the drug's peak level (highest concentration) or at the drug's trough level (lowest concentration). Peak levels are useful when testing for toxicity, and trough levels are useful for demonstrating a satisfactory therapeutic level.

Transport and Processing of Blood Specimens

Once blood specimens are obtained, they should be promptly transported to the laboratory. Because the blood cells continue to live in the collection tubes, they will metabolize some of the components in the blood. This can result in alterations in the concentration of some blood components before analysis in the laboratory. Therefore blood specimens should be delivered to the laboratory for processing within 1 hour, depending on the test. Stat specimens should be delivered immediately after being drawn. Laboratories have written criteria for rejecting a specimen as unsuitable for testing. Box 2-1 lists common reasons for rejecting a blood specimen.

In general, specimens should be tested within 1 hour of collection. If this is not possible, the sample may need to be refrigerated or frozen depending on the compound for testing. Some blood specimens must be sent by mail or special courier from physicians' offices or small hospitals to large reference laboratories. As a result, delays of 24 hours may occur before specimen analysis.

After testing, the remainder of the blood sample should be saved by the laboratory along with the original sample for 24 hours to be retested if needed to verify discrepant results. These samples can also be used for additional (“add-on”) tests ordered by the physician while avoiding additional venipunctures. With retesting or “add-on” requests, the stability of the requested serum constituent becomes an important consideration.

Multiphasic screening machines can perform many blood tests quickly and simultaneously using a very small blood sample. An example is the Astra-7 or Chem-7, which usually includes the following seven studies: sodium, potassium, chloride, CO₂ content, BUN, creatinine, and glucose. See Appendix C for a listing of common panels. The basic metabolic panel and comprehensive metabolic panel have replaced the Chem-7 and Astra panels. These changes are the result of the recent federal guidelines to standardize the nomenclature for chemistry panels. The advantage of these machines is that results are available quickly and the cost is cheaper when compared to performing each test individually.

Reporting of Results

Although accuracy and processing are the prerequisites of good laboratory practice, timeliness in reporting results is essential. To be clinically useful, a test result must be reported promptly. Delays in reporting a result can make the data useless and potentially could be life-threatening to the patient. Verbal reporting of result to the clinician should be provided by a licensed health care provider after using two patient identifiers (e.g., patient's name and medical record number/date of birth). A “read-back” of the information from the clinician should also occur.

The report must also be entered in the appropriate medical record and must be presented in a manner that is clear and easily interpreted. A listing of the patient's medications will help with test result interpretation.

The results should include the test results, reporting units, and reference ranges. It is important to note that normal ranges for laboratory tests vary from institution to institution. Often serial listing of results is useful for tests in which trends and values make interpretation easier. Comments may be added to help interpret test results; for example, the technologist would indicate if the sample was hemolyzed.

Because acronyms are used to shorten test names, these code names must be understood for proper interpretation. For example, the acronym LAP could stand for leucine amino peptidase or for leukocyte alkaline phosphatase.

Proper reporting of a “critical” or “panic” value is essential. These values are results well outside the usual range of normal and generally require immediate intervention. Common examples are shown in Box 2-2. If these results were phoned to a physician or nurse, verification of this notification must be properly documented.

BOX 2-2 Adult Critical Laboratory Values ^∗

Bicarbonate (Total CO₂)	<10 or >40 mmol/L
Bilirubin, total	>15 mg/dL
Blood culture	Positive
Calcium	<6 or >13 mg/dL
Digoxin	>2.4 ng/mL
Direct Coombs	Positive
Glucose	<40 or >450 mg/dL
Glucose, point of care (Chemstrip)	≤60 or ≥450 mg/dL
Hematocrit	≤21% or ≥65%
Hemoglobin	≤7 or ≥21g/dL
Magnesium	≤1 or ≥9 mg/dL
Partial thromboplastin time	≥85 seconds
PCO₂	≤20 or ≥60 mm Hg
pH	≤7.25 or ≥7.6
Platelet count	<20,000 or >1,000,000 /mcL
PO₂	≤40 mm Hg
Potassium	<3 or >6.1 mmol/L
Prothrombin time/International Normalized Ratio (INR)	≥5
Sodium	<120 or >160 mmol/L
Theophylline, trough	>25 mcg/mL
Tobramycin, peak	>12 mcg/mL
Tobramycin, trough	>2 mcg/mL
White blood cell count	≤2,000 or ≥40,000/mcL

^∗Critical values should be reported to the treating health care provider immediately so therapeutic action can be instigated.

Acetylcholine Receptor Antibody Panel (AChR Ab, Anti–AChR Antibody)

Normal Findings

ACh receptor (muscle) binding antibodies: ≤0.02 nmol/L

ACh receptor (muscle) modulating antibodies: 0-20% (reported as % loss of AChR)

Striational (striated muscle) antibodies: <1:60

Indications

Antibodies to AChR are used to diagnose acquired myasthenia gravis (MG) and also to monitor patient response to immunosuppressive therapy.

Test Explanation

These antibodies may cause blocks in neuromuscular transmission by interfering with the binding of acetylcholine (ACh) to ACh receptor (AChR) sites on the muscle membrane, thereby preventing muscle contraction. It is this phenomenon that characterizes myasthenia gravis (MG). Myasthenia gravis (MG) is an autoimmune disease usually caused by antibodies that block or destroy receptors for the neurotransmitter acetylcholine, leading to muscle weakness and fatigue. Antibodies to AChR occur in more than 85% to 90% of patients with acquired MG, and 63% of patients with only ocular MG have elevated levels. The presence of these antibodies is virtually diagnostic of MG, but a negative test does not exclude the disease. The measured titers do not correspond well with the severity of MG. In an individual patient with MG, however, antibody levels are particularly useful in monitoring response to immunosuppressive or plasmapheresis therapy. As the patient improves, antibody titer decreases.

In adults with MG, there is at least a 20% occurrence of thymoma or other neoplasm. Neoplasms are an endogenous source of the antigens driving production of AChR autoantibodies. Among patients who have a thymoma, 59% have MG. Because congenital MG is not an autoimmune disease, this antibody test is not helpful in the diagnosis of congenital MG.

There are several AChR antibodies that can be associated with MG binding, blocking, and modulating antibodies. The AChR-binding antibody can activate complement and lead to loss of AChR. The AChR-binding antibody is most commonly used. The AChR-modulating antibody causes receptor endocytosis resulting in loss of AChR expression, which correlates most closely with clinical severity of disease. It is most sensitive. A positive modulating antibody test may indicate subclinical MG, contraindicating the use of curare-like drugs during surgery. Approximately 10% to 15% of individuals with confirmed myasthenia gravis have no measurable binding, blocking, or modulating antibodies. The AChR-blocking antibody may impair binding of acetylcholine to the receptor, leading to poor muscle contraction. It is the least sensitive test (positive in only 61% of patients with MG), but it can be quantified more accurately. The blocking and modulating antibodies are not often positive for about 1 year after onset of MG symptoms.

The most commonly used method for the detection of these AChR antibodies is the Quantitative Radioimmunoassay/Semi-Quantitative Radioreceptor Assay.

Anti-Striated Muscle Antibody (Striated Muscle Antibody, IgG) titers greater than or equal to 1:80 are suggestive of myasthenia. This antibody is detectable in 30% to 40% of anti-AChR-negative patients (particularly those with bulbar symptoms only). However, striated muscle antibody can be found in rheumatic fever, myocardial infarction, and a variety of post-cardiotomy states.

Interfering Factors

• False-positive results may occur in patients with amyotrophic lateral sclerosis who have been treated with cobra venom.

• False-positive results may be seen in patients with penicillamine-induced or Lambert-Eaton myasthenic syndromes.

• Patients with autoimmune liver disease may have elevated results.

The use of muscle relaxant drugs (metocurine and succinylcholine) or penicillamine may cause false-positive results.

Immunosuppressive drugs may suppress the formation of these antibodies in patients with subclinical MG.

Procedure and Patient Care

Before

Explain the procedure to the patient.

Tell the patient that no fasting is required.

Inform the patient that the blood sample is usually sent to a reference laboratory. It will take several days before the results are available.

During

• Collect a venous blood sample in a red-top tube.

After

• Apply pressure or a pressure dressing to the venipuncture site.

• Assess the venipuncture site for bleeding.

Test Results and Clinical Significance

Increased Levels

MG,

Ocular MG,

Thymoma:

Fifty-nine percent of patients with thymoma have MG and 10% of MG patients have a thymoma.

Related Tests

Cholinesterase (p. 159). Patients with an acquired or congenital deficiency of this enzyme will experience acute MG-like muscle paralysis when a depolarizing agent, such as succinylcholine, is used for anesthesia induction.

Electromyography (p. 554). Repetitive stimulation or single-fiber electromyogram is positive in 90% of MG patients.

Chest x-ray (p. 1014) or chest CT (p. 1029). These tests are used to identify thymoma.

Acid Phosphatase (Prostatic Acid Phosphatase [PAP], Tartrate-Resistant Acid Phosphatase [TRAP])

Normal Findings

Adult/elderly: 0.13-0.63 units/L (Roy, Brower, Hayden, 37° C) or 2.2-10.5 units/L (SI units)

Child: 8.6-12.6 units/mL (30° C)

Newborn: 10.4-16.4 units/mL (30° C)

Indications

Total acid phosphatase and specifically the PAP isoenzyme is primarily used to document rape cases. It was used in the diagnosis of prostate cancer, but has been replaced by the use of prostate specific antigen (PSA, p. 420). Otherwise this test has very little clinical usefulness.

Test Explanation

Acid phosphatase is found in many tissues, including liver, red blood cells, bone marrow, and platelets. The highest levels are found in the prostate gland—the PAP isoenzyme. Usually (but not always) elevated levels are seen in patients with prostatic cancer, especially if it has metastasized beyond the capsule to other parts of the body.

Because acid phosphatase is also found at high concentrations in seminal fluid, this test can be performed on vaginal secretions to investigate alleged rape. This is now the primary use of PAP testing. High levels of acid phosphatase also exist in white blood cells (mostly monocytes and lymphocytes). They are helpful in determining the clinical course of patients with lymphoproliferative diseases and hairy cell leukemia. Acid phosphatase is a lysosomal enzyme; therefore lysosomal storage diseases (such as Gaucher disease and Niemann-Pick disease) are associated with elevated levels.

Interfering Factors

• Falsely high levels of acid phosphatase (and specifically PAP) may occur in males after a digital rectal examination or after instrumentation of the prostate (e.g., cystoscopy) because of prostatic stimulation. Elevated levels of 25% to 50% may occur for up to 48 hours after prostate manipulation. The test should be repeated if elevated levels occur after a rectal or prostate examination.

• Alkaline and acid phosphatase are very similar enzymes that function at different pH levels. Any condition associated with very high levels of alkaline phosphatase may falsely indicate high acid phosphatase levels.

Drugs that may cause increased levels of acid phosphatase include alglucerase, androgens (in females), and clofibrate (Atromid-S).

Drugs that may cause decreased levels include alcohol, fluorides, heparin, oxalates, and phosphates.

Procedure and Patient Care

Before

Explain the procedure to the patient.

Tell the patient that no food or drink restrictions are necessary.

• Note that some laboratories request notification before the blood sample is drawn so that immediate attention (<1 hour) can be given to the sample.

During

• Collect a venous blood sample in a red-top tube.

• Avoid hemolysis. RBCs contain acid phosphatase.

• Note on the laboratory slip if the patient has had a prostatic or rectal examination or instrumentation of the prostate within the past 24 to 48 hours.

After

• Apply pressure or a pressure dressing to the venipuncture site.

• Assess the venipuncture site for bleeding.

• Promptly deliver the specimen to the laboratory.

• Do not leave the specimen at room temperature for 1 hour or longer; the enzyme is heat and pH sensitive, and acid phosphatase activity will decrease. Once the specimen is received by the laboratory, the use of a preservative and prompt refrigeration are important.

Test Results and Clinical Significance

Increased Levels

Prostatic carcinoma,

Benign prostatic hypertrophy,

Prostatitis:

Acid phosphatase and specifically PAP exist in the lysosomes of prostate cells. Diseases affecting prostate tissue will destroy those cells, and the lysosomal contents will spill into the bloodstream, where they will be detected.

Multiple myeloma,

Paget disease,

Hyperparathyroidism,

Metastasis to the bone:

Because acid phosphatase exists in the lysosomes of the bone marrow, diseases affecting the bone will be associated with elevated blood levels.

Multiple myeloma,

Sickle cell crisis,

Thrombocytosis:

Because acid phosphatase exists in the lysosomes of blood cells, diseases affecting blood cells will be associated with elevated blood levels.

Lysosomal disorders (e.g., Gaucher disease): Because acid phosphatase exists in the lysosomes of many tissues affected by these diseases, elevated blood levels can be expected.

Renal diseases,

Liver diseases, such as cirrhosis:

Because acid phosphatase is present in these organs, diseases affecting these organs will be associated with elevated blood levels.

Rape:

PAP will be elevated in vaginal secretions of a woman having been recently raped. The PAP assay is a well-documented presumptive assay for the presence of semen.

Related Tests

Prostate Specific Antigen (PSA) (p. 420). This is a more specific test for prostatic cancer.

Alkaline Phosphatase (p. 47). This is a similar enzyme that is more easily identified in an alkaline environment. It is useful in the evaluation of diseases of the liver and bone.

Activated Clotting Time (ACT, Activated Coagulation Time)

Normal Findings

70-120 seconds

Therapeutic range for anticoagulation: 150-600 seconds

(Normal ranges and anticoagulation ranges vary according to particular therapy.)

Indications

The ACT is primarily used to measure the anticoagulant effect of heparin or other direct thrombin inhibitors during cardiac angioplasty, hemodialysis, and cardiopulmonary bypass (CPB) surgery.

Test Explanation

This test measures the time for whole blood to clot after the addition of particulate activators. Like the activated partial thromboplastin time (aPTT, p. 383), it measures the ability of the intrinsic pathway (reaction 1) to begin clot formation by activating factor XII (see Figure 2-12, p. 167). By checking the blood clotting status with ACT, the response to unfractionated heparin therapy can be easily and rapidly monitored. Equally important is the use of the ACT in determining the appropriate dose of protamine sulfate required to reverse the effect of heparin on completion of surgical procedures and hemodialysis.

Both the aPTT and the ACT can be used to monitor heparin therapy in patients on CPB. However, the ACT has several advantages over the aPTT. First, the ACT is more accurate than the aPTT when high doses of heparin are used for anticoagulation. This makes it especially useful during clinical situations requiring high-dose heparin, such as during CPB when high-dose anticoagulation is necessary at levels 10 times those used for venous thrombosis. The aPTT is not measurable at these high doses. The accepted goal for the ACT is 400-480 seconds during CPB.

Second, the ACT is not only less expensive, but it is also more easily and rapidly performed than the aPTT, which is time consuming and requires full laboratory facilities. The ACT can be performed at the bedside. This provides immediate information on which further therapeutic anticoagulation decisions can be based. The capability to perform the ACT at the “point of care” makes the ACT particularly useful for patients requiring angioplasty, hemodialysis, and CPB.

A nomogram adjusted to the patient's baseline ACT is often used as a guide to reach the desired level of anticoagulation during these procedures. This same nomogram is used in determining the dose of protamine to be administered to neutralize the heparin when a return to normal coagulation is desired on completion of these procedures. The ACT is used in determining when it is safe to remove the vascular access after these procedures. The modified ACT test requires a smaller-volume blood specimen, automated blood sampling, standardized blood/reagent mixing, and faster clotting time results than the conventional ACT. The modified ACT is now being used more frequently.

Interfering Factors

• The ACT is affected by several biologic variables, including hypothermia, hemodilution, and platelet number and function.

• Factors affecting the pharmacokinetics of heparin (e.g., kidney or liver disease) and heparin resistance due to antithrombin deficiency and contact factor deficiencies can affect ACT measurements.

• A partially or completely occluded specimen can increase ACT measurements.

Procedure and Patient Care

Before

Explain the procedure to the patient.

During

• Less than 1 mL of blood is collected into a commercial container. This container is then placed into a whole blood microcoagulation analyzer at the bedside. When a clot is formed, the ACT value is displayed on the machine's panel.

• If the patient is receiving a continuous heparin drip, the blood sample is obtained from the arm without the intravenous catheter.

After

• Apply pressure to the venipuncture site. Remember that the bleeding time will be prolonged because of anticoagulation therapy.

• Assess the patient to detect possible bleeding. Check for blood in the urine and all other excretions and assess the patient for bruises, petechiae, and low back pain.

• For clinical significance, the test results must be correlated with the time of heparin administration. A clinical flow sheet is used to list the test results with the time and route of heparin administration.

Test Results and Clinical Significance

Increased Levels

Heparin administration: Heparin, along with antithrombin III, interrupts in the action of several coagulation proteins (except factor VII). As a result, the intrinsic pathway of coagulation is inhibited. This pathway is measured by the ACT and is therefore prolonged.

Clotting factor deficiencies: Deficiencies in any clotting factor associated with the intrinsic pathway will be associated with prolonged ACT.

Cirrhosis of the liver: Coagulation factors are proteins that are synthesized in the liver. Liver pathology therefore is associated with a reduction in coagulation factors; this prolongs the time required for the reactions of the intrinsic pathway and prolongs the ACT.

Coumadin administration: Deficiencies in the vitamin K clotting factors associated with the intrinsic pathway will cause a prolonged ACT.

Lupus inhibitor: Lupus inhibitors are autoantibodies against components involved in the activation of the coagulation cascade and thus prolong the ACT.

Decreased Levels

Thrombosis: In thrombotic syndromes in which secondary hemostasis is inappropriately stimulated, the ACT may be shortened.

Related Tests

Partial Thromboplastin Time (PTT) (p. 383). The PTT is another test used to evaluate the intrinsic pathway of secondary hemostasis. It, too, is commonly used to monitor heparin therapy.

Prothrombin Time (p. 434). The PT is used to evaluate the extrinsic and common pathways of secondary hemostasis.

Coagulating Factor Concentration (p. 163). This is a quantitative measurement of specific coagulation factors.

Adrenal Steroid Precursors (Androstenediones [AD], Dehydroepiandrosterone [DHEA], Dehydroepiandrosterone Sulfate [DHEA S], 11-Deoxycortisol, 17-Hydroxyprogesterone, 17-Hydroxypregnenolone, Pregnenolone)

Normal Findings

Indications

This test is used for evaluating virilizing syndromes and amenorrhea.

Test Explanation

Androstenediones (ADs, DHEA, and the sulfuric ester, DHEA S) are precursors of testosterone and estrone, and are made in the gonads and the adrenal gland. 11-Deoxycortisol, 17-hydroxyprogesterone, 17-hydroxypregnenolone, and pregnenolone are precursors of cortisol. ACTH stimulates their adrenal secretion. Children with congenital adrenal hyperplasia (CAH) have genetic mutations that cause deficiencies in the enzymes involved in the synthesis of cortisol, testosterone, aldosterone, and estrone. When defects in enzyme synthesis occur along the path of hormone synthesis, the listed precursors exists in levels that exceed normal through the increased stimulation of ACTH. In most cases, CAH is a genetic autosomal recessive disorder.

The symptoms of this disorder depend on which steroids are overproduced and which are deficient. As a result, CAH may present with various symptoms, including virilization of the affected female infant, signs of androgen excess in males and females, signs of sex hormone deficiency in males and females, salt-wasting crisis secondary to cortisol and aldosterone deficiency, or hormonal hypertension caused by increased mineralocorticoids. A milder, nonclassic form of CAH is characterized by premature puberty, acne, hirsutism, menstrual irregularity, and infertility.

These same precursors can occur in adults because of adrenal or gonadal tumors that produce one of these precursors. Patients with polycystic ovary (Stein-Leventhal) syndrome have particularly elevated levels of ADs. Levels of DHEA S are particularly high in patients with adrenal carcinoma.

In patients suspected of CAH, testing for a panel of steroids involved in the cortisol biosynthesis pathway may be performed to establish the specific enzyme deficiency. In most cases, basal concentrations within the normal reference interval rule out CAH. The ratio of the precursor to the final pathway product (with and without ACTH stimulation) may be used to diagnose which enzyme is deficient.

Testing is performed by Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry. Results vary considerably based on testing method.

Interfering Factors

• A radioactive scan performed 1 week before the test may invalidate the test results, if it is performed by radioimmunoassay.

Drugs that may increase levels of androstenedione are clomiphene, corticotropin, and metyrapone.

Steroids may decrease levels of androstenedione.

Procedure and Patient Care

Before

Explain the procedure to the patient.

Tell the patient that the specimen should be collected 1 week before or after the menstrual period.

• Note that fasting is preferable.

• Because peak production of androstenedione is around 7 AM, blood should be drawn around that time.

During

• Collect a venous blood sample in a red-top or gold-top tube.

• Indicate the date of the last menstrual period on the laboratory form.

After

• Apply pressure or a pressure dressing to the venipuncture site.

• Assess the venipuncture site for bleeding.

Test Results and Clinical Significance

Increased Levels

Adrenal tumor: Some tumors make large amounts of androstenediones, which is then converted by the ovaries and fatty tissue to testosterone and estrogen. The relatively high level of testosterone causes the virilizing signs.

Congenital adrenal hyperplasia: This disease is characterized by enzyme defects that prevent conversion of androstenediones to cortisol. Androstenediones levels are increased.

Ectopic ACTH-producing tumors,

Cushing disease:

ACTH stimulates the adrenal gland to make large amounts of hormones, including androstenediones.

Cushing syndrome: Large amounts of hormones, including androstenediones, are made in the adrenal gland.

Stein-Leventhal syndrome

Ovarian sex cord tumor

Decreased Levels

Primary or secondary adrenal insufficiency,

Ovarian failure,

Oophorectomy:

There is a decreased production and conversion of androstenediones.

Related Tests

Testosterone (p. 476). This is a direct measurement of testosterone.

Estradiol (p. 226). This is a direct measurement of one of the conjugated estrogens.

Cortisol, Blood (p. 179). This is a direct measurement of cortisol, the major adrenal glucocorticosteroid.

Adrenocorticotropic Hormone (ACTH, Corticotropin)

Normal Findings

Adult/elderly:

Female: 19 years and older: 6-58 pg/mL

Male: 19 years and older: 7-69 pg/mL

Children:

Male and female: 10-18 years: 6-55 pg/mL

Male and female: 1 week-9 years: 5-46 pg/mL

Indications

The serum ACTH study is a test of anterior pituitary gland function that affords the greatest insight into the causes of either Cushing syndrome (overproduction of cortisol) or Addison disease (underproduction of cortisol).

Test Explanation

An elaborate feedback mechanism for cortisol coordinates the function of the hypothalamus, pituitary gland, and adrenal glands. ACTH is an important aspect of this mechanism. Corticotropin-releasing hormone (CRH) is made in the hypothalamus. This stimulates ACTH production in the anterior pituitary gland, which in turn stimulates the adrenal cortex to produce cortisol. The rising levels of cortisol act as negative feedback and curtail further production of CRH and ACTH.

In the patient with Cushing syndrome, an elevated ACTH level can be caused by a pituitary ACTH-producing tumor or a nonpituitary (ectopic) ACTH-producing tumor, usually in the lung, pancreas, thymus, or ovary. ACTH levels greater than 200 pg/mL usually indicate ectopic ACTH production. If the ACTH level is below normal in a patient with Cushing syndrome, an adrenal adenoma or carcinoma is probably the cause of the hyperfunction (Table 2-2).

TABLE 2-2

Cortisol/ACTH Levels in Diagnosis of Adrenal Dysfunction

Disease	Cortisol Level	ACTH Level
Cushing syndrome Adrenal micronodular hyperplasia Adrenal tumor (adenoma, cancer)	High	Low
Cushing syndrome Cushing disease (ACTH-producing pituitary tumor )Ectopic ACTH-producing tumor (e.g., lung cancer)	High	High
Addison disease Adrenal gland failure (e.g., infarction, hemorrhage, congenital adrenal hyperplasia)	Low	High
Hypopituitarism	Low	Low

In patients with Addison disease, an elevated ACTH level indicates primary adrenal gland failure, as in adrenal gland destruction caused by infarction, hemorrhage, or autoimmunity; surgical removal of the adrenal gland; congenital enzyme deficiency; or adrenal suppression after prolonged ingestion of exogenous steroids. If the ACTH level is below normal in a patient with adrenal insufficiency, hypopituitarism is most probably the cause of the hypofunction (see Table 2-2).

ACTH can be directly measured by Quantitative Chemiluminescent Immunoassay. ACTH levels exhibit diurnal variations that correspond to cortisol levels. Levels in evening (8 PM to 10 PM) samples are usually one half to two thirds those of morning (4 AM to 8 AM) specimens. This diurnal variation is lost when disease (especially neoplasm) affects the pituitary or adrenal glands. Likewise stress can blunt or eliminate this normal diurnal variation.

ACTH is measured in amniotic fluid when anencephaly is suspected. Decreased levels are noted in anencephalic fetuses (see discussion of amniocentesis on p. 632).

Interfering Factors

• Stress (trauma, pyrogen, hypoglycemia), menses, and pregnancy cause increased levels of cortisol. This is accomplished through elevation of ACTH.

Recently administered radioisotope scans can affect levels measured by radioimmunoassay or immunoradiometry.

Drugs that may cause increased levels include aminoglutethimide, amphetamines, estrogens, ethanol, insulin, levodopa, metyrapone, spironolactone, and vasopressin.

Exogenously administered corticosteroids decrease ACTH levels.

Clinical Priorities

• Evaluate the patient for stress factors that could invalidate test results.

• Remember that there is a diurnal variation in ACTH levels that corresponds to cortisol levels. With a normal sleep pattern, levels are highest in the morning and lowest in the evening.

Procedure and Patient Care

Before

Explain the procedure to the patient. Allow plenty of time to answer questions so the patient's stress is diminished as much as possible.

Keep the patient on nothing by mouth (NPO) status after midnight the day of the test.

• Evaluate the patient for stress factors that could invalidate the test results.

• Evaluate the patient for sleep pattern abnormalities. With a normal sleep pattern, the ACTH level is highest between 4 AM and 8 AM and lowest around 9 PM.

• Assess the patient for self-administration of drugs that could affect test results.

During

• Collect a venous blood sample in a lavender (EDTA) or pink-top (K₂ EDTA) tube or as required by your reference laboratory.

• Chill the blood tube to prevent enzymatic degradation of ACTH.

After

• Place the specimen in ice water and send it to the chemistry laboratory immediately. ACTH is a very unstable peptide in plasma and should be stored at −20° C to prevent artificially low values.

• Apply pressure or a pressure dressing to the venipuncture site.

• Assess the venipuncture site for bleeding.

Test Results and Clinical Significance

Increased Levels

Addison disease (primary adrenal insufficiency),

Adrenogenital syndrome (congenital adrenal hyperplasia):

The adrenal glands are not making enough cortisol for the body's needs. The reduced serum cortisol level is a strong stimulus to pituitary production of ACTH.

Cushing disease (pituitary-dependent adrenal hyperplasia),

Ectopic ACTH syndrome,

Stress:

ACTH is overproduced as a result of neoplastic overproduction of ACTH in the pituitary or elsewhere in the body by an ACTH-producing cancer. Stress is a potent stimulus to ACTH production.

Decreased Levels

Secondary adrenal insufficiency (pituitary insufficiency),

Hypopituitarism:

The pituitary gland is incapable of producing adequate ACTH.

Adrenal adenoma or carcinoma,

Cushing syndrome,

Exogenous steroid administration:

Overproduction or availability of cortisol is a strong inhibitor to pituitary production of ACTH.

Related Tests

Cortisol, Blood, and Urine (pp. 179 and 920). Cortisol is a hormone produced by the adrenal gland and is the main determinant of Cushing syndrome (overproduction) or Addison disease (underproduction).

Adrenocorticotropic Hormone (ACTH) Stimulation (p. 34). This test is used to determine the cause of adrenal insufficiency.

Dexamethasone Suppression (p. 204). This test is used to determine the cause of Cushing syndrome.

Adrenocortotropic Hormone Stimulation With Metyrapone (p. 36). This test is used to determine the cause of Cushing syndrome.

Adrenocorticotropic Hormone Stimulation (ACTH Stimulation With Cosyntropin, Cortisol Stimulation)

Normal Findings

Rapid test: cortisol levels increase >7 mg/dL above baseline

24-hour test: cortisol levels >40 mcg/dL

3-day test: cortisol levels >40 mcg/dL

Indications

This test evaluates the ability of the adrenal gland to respond to ACTH administration. It is useful in evaluating the cause of adrenal insufficiency and also in evaluating patients with cushingoid symptoms.

Test Explanation

This test is performed on patients found to have adrenal insufficiency. An increase in plasma cortisol levels after the infusion of an ACTH-like drug indicates that the adrenal gland is normal and capable of functioning if stimulated. In that case the cause of adrenal insufficiency would lie within the pituitary gland (hypopituitarism, which is called secondary adrenal insufficiency). If little or no rise in cortisol levels occurs after the administration of the ACTH-like drug, the adrenal gland is the source of the problem and cannot secrete cortisol. This is called primary adrenal insufficiency (Addison disease), which may be caused by adrenal hemorrhage, infarction, autoimmunity, metastatic tumor, surgical removal of the adrenal glands, or congenital adrenal enzyme deficiency.

This test can also be used to evaluate patients with Cushing syndrome. Patients with Cushing syndrome caused by bilateral adrenal hyperplasia have an exaggerated cortisol elevation in response to the administration of the ACTH-like drug. Those experiencing Cushing syndrome as a result of hyperfunctioning adrenal tumors (which are usually autonomous and relatively insensitive to ACTH) have little or no increase in cortisol levels over baseline values.

Cosyntropin (Cortrosyn) is a synthetic subunit of ACTH that has the same corticosteroid-stimulating effect as endogenous ACTH in healthy persons. During this test, cosyntropin is administered to the patient, and the ability of the adrenal gland to respond is measured by plasma cortisol levels.

The rapid stimulation test is only a screening test. A normal response excludes adrenal insufficiency. An abnormal response, however, requires a 1- to 3-day prolonged ACTH stimulation test to differentiate primary insufficiency from secondary insufficiency. It should be noted that the adrenal gland can also be stimulated by insulin-induced hypoglycemia as a stressing agent. When insulin is the stimulant, cortisol and glucose levels are measured.

Interfering Factors

Drugs that may cause artificially increased cortisol levels include prolonged corticosteroid administration, estrogens, and spironolactone.

Procedure and Patient Care

Before

Have the patient remain on nothing by mouth (NPO) status after midnight the day of the test.

During

Rapid Test

• Obtain a baseline plasma cortisol level less than 30 minutes before cosyntropin administration.

• Administer an intravenous (IV) injection of cosyntropin over a 2-minute period. An intramuscular (IM) injection may also be used.

• Measure plasma cortisol levels 30 and 60 minutes after drug administration. Serum or heparinized blood is acceptable.

24-Hour Test

• Obtain a baseline plasma cortisol level.

• Start an IV infusion of synthetic cosyntropin for administration over 24 hours.

• After 24 hours, obtain another plasma cortisol level.

3-Day Test

• Obtain a baseline plasma cortisol level.

• Administer cosyntropin intravenously over an 8-hour period on 2 to 3 consecutive days.

• Plasma cortisol is then measured at 12, 24, 36, 48, 60, and 72 hours after the start of the test.

After

• Apply pressure or a pressure dressing to the venipuncture site.

• Check the venipuncture site for bleeding.

Test Results and Clinical Significance

Exaggerated Response

Cushing syndrome: Bilateral adrenal hyperplasia.

Adrenal insufficiency: Secondary adrenal insufficiency caused by hypopituitarism, exogenous steroid ingestion, or endogenous steroid production from nonendocrine tumor.

Normal or Below-Normal Response

Cushing syndrome: Adrenal adenoma, adrenal carcinoma, ACTH-producing tumor, chronic steroid ingestion.

Adrenal insufficiency: Primary adrenal insufficiency (Addison disease) caused by adrenal infarction, hemorrhage, infection, or metastatic tumor to adrenal gland.

Congenital enzyme adrenal insufficiency, surgical removal of adrenal gland, and ingestion of drugs, such as mitotane, metyrapone, or aminoglutethimide.

Related Tests

Cortisol (p. 179). Cortisol is a hormone produced by the adrenal gland and is the main determinant of Cushing syndrome (overproduction) or Addison disease (underproduction).

Adrenocorticotropic Hormone (ACTH) (p. 31). This test is used to determine the cause of Cushing syndrome or Addison disease.

Dexamethasone Suppression (p. 204). This test is used to determine the cause of Cushing syndrome.

Adrenocortotropic Hormone Stimulation With Metyrapone (see following test). This test is used to determine the cause of Cushing syndrome.

Adrenocorticotropic Hormone Stimulation With Metyrapone (Metyrapone, ACTH Stimulation With Metyrapone)

Normal Findings

24-Hour Urine

Baseline excretion of urinary 17-hydroxycorticosteroid (OCHS) more than doubled

Blood

11-Deoxycortisol increased to >7 mcg/dL and cortisol <10 mcg/dL

Indications

This test is useful in differentiating adrenal hyperplasia from a primary adrenal tumor by determining whether the pituitary-adrenal feedback mechanism is intact.

Test Explanation

Metyrapone (Metopirone) is a potent blocker of an enzyme involved in cortisol production. Cortisol production is therefore reduced. When this drug is given, the resulting decrease in cortisol production should stimulate pituitary secretion of adrenocorticotropic hormone (ACTH) by way of a negative-feedback mechanism. Cortisol itself cannot be synthesized because of the metyrapone inhibition at the 11-beta-hydroxylation step, but an abundance of cortisol precursors (11-deoxycortisol and OCHS) will be formed. These cortisol precursors can be detected in the urine or in the blood. This test is similar to the ACTH stimulation test.

In patients with adrenal hyperplasia caused by pituitary overproduction of ACTH, the cortisol precursors are greatly increased. This is because the normal adrenal-pituitary feedback response mechanism is still intact. No response to metyrapone occurs in patients with Cushing syndrome resulting from adrenal adenoma or carcinoma, because the tumors are autonomous and therefore insensitive to changes in ACTH secretion. This test has no significant advantage over the ACTH stimulation test in the differential diagnosis of Cushing disease.

This test is also used to evaluate the pituitary reserve capacity to produce ACTH. It can document that adrenal insufficiency exists as a result of pituitary disease (secondary adrenal insufficiency) rather than primary adrenal pathology. This test should not be performed if primary adrenal insufficiency is likely. A severe, life-threatening adrenal crisis could be precipitated. A normal response to ACTH should be demonstrated before metyrapone is given.

Contraindications

• Patients with possible primary adrenal insufficiency, because metyrapone could reduce the production of what little cortisol is produced and precipitate an adrenal crisis.

• Patients taking glucocorticoids.

Potential Complications

• Addison disease and addisonian crisis, because metyrapone inhibits cortisol production

Interfering Factors

• Recent administration of radioisotopes can interfere with test results performed by radioimmunoassay (RIA).

Chlorpromazine (Thorazine) interferes with the response to metyrapone and should not be administered during the testing.

Clinical Priorities

• This test evaluates the intactness of the pituitary-adrenal feedback mechanism.

• This test should not be performed on patients with adrenal insufficiency. A severe, life-threatening adrenal or addisonian crisis could result.

• Patients should be carefully assessed for impending signs of addisonian crisis, which include glucocorticoid deficiency, drop in extracellular fluid volume, and hyperkalemia. This is a medical emergency and must be treated vigorously.

Procedure and Patient Care

Before

Explain the procedure to the patient.

• Obtain a baseline 24-hour urine specimen for 17-OCHS level for the urine test.

• Obtain a baseline cortisol level (see p. 179) for the blood test.

During

Blood

• Administer a prescribed dose of metyrapone at 11 PM the night before the blood specimen is to be collected. Collect a blood specimen in the morning.

Urine

• Obtain a 24-hour urine specimen for a 17-OCHS baseline level. Then collect a 24-hour urine specimen for the 17-OCHS level during and again 1 day after the oral administration of a dose of metyrapone, which may be given every 4 hours for 24 hours.

After

• Assess the patient for impending signs of addisonian crisis (muscle weakness, mental and emotional changes, anorexia, nausea, vomiting, hypotension, hyperkalemia, vascular collapse).

• Note that addisonian crisis is a medical emergency that must be treated vigorously. Basically, the immediate treatment includes replenishing steroids, reversing shock, and restoring blood circulation.

Test Results and Clinical Significance

Increased Levels

Adrenal hyperplasia: Cortisol precursors will be significantly increased as a result of accentuating the ACTH effect.

Adrenal tumor: Tumors are autonomous and are not affected by inhibitory or stimulatory feedback. There is no apparent change in cortisol precursors.

Ectopic ACTH syndrome: This syndrome occurs when neoplasms (usually lung cancer) produce ACTH without regard to regulatory mechanisms. There is no apparent change in cortisol precursors.

Secondary adrenal insufficiency: There will be no significant change in cortisol precursors, because there is no pituitary function to stimulate the production of ACTH.

Related Tests

Adrenocorticotropic Hormone (ACTH) (p. 31). This is a direct measurement of ACTH, which is used in the evaluation of Cushing syndrome and Addison disease.

Adrenocorticotropic Hormone (ACTH) Stimulation (p. 34). This test is used similarly to the metyrapone test for evaluation of Addison disease and Cushing syndrome.

Age-Related Macular Degeneration Risk Analysis (Y402H and A69S)

Normal Findings

No mutation noted.

Indications

This test is used for risk assessment and as supportive documentation of macular degeneration.

Test Explanation

This information can be clinically useful when making medical management decisions (e.g., the use of inflammatory markers) and emphasizing to patients the benefits of smoking cessation and dietary modification. In some cases, genotype information may also assist with clinical diagnosis.

Procedure and Patient Care

Before

Explain the procedure to the patient.

During

• Collect a venous sample of blood in a lavender- (EDTA) or a yellow-top (ACD) tube.

After

• Apply pressure to the venipuncture site.

Tell the patient that results may not be available for a few weeks.

Abnormal Findings

Increased

ARMD—Patients with abnormal genetics as described are at a marked increased risk for developing macular degeneration.

Alanine Aminotransferase (ALT, formerly Serum Glutamic-Pyruvic Transaminase [SGPT])

Normal Findings

Elderly: may be slightly higher than adult values

Adult/child: 4-36 international units/L at 37° C or 4-36 units/L (SI units)

Values may be higher in men and in African Americans.

Infant: may be twice as high as adult values

Indications

This test is used to identify hepatocellular diseases of the liver. It is also an accurate monitor of improvement or worsening of these diseases. In jaundiced patients an abnormal alanine aminotransferase (ALT) will incriminate the liver rather than red blood cell (RBC) hemolysis as a source of the jaundice.

Test Explanation

ALT is found predominantly in the liver; lesser quantities are found in the kidneys, heart, and skeletal muscle. Injury or disease affecting the liver parenchyma will cause a release of this hepatocellular enzyme into the bloodstream, thus elevating serum ALT levels. Most ALT elevations are caused by liver dysfunction. Therefore this enzyme is not only sensitive but also quite specific for hepatocellular disease. In hepatocellular disease other than viral hepatitis the ALT/AST (aspartate aminotransferase) ratio (DeRitis ratio) is less than 1. In viral hepatitis the ratio is greater than 1. This is helpful in the diagnosis of viral hepatitis.

Interfering Factors

Previous intramuscular (IM) injections may cause elevated levels.

Drugs that may cause increased ALT levels include acetaminophen, allopurinol, aminosalicylic acid, ampicillin, azathioprine, carbamazepine, cephalosporins, chlordiazepoxide, chlorpropamide, clofibrate, cloxacillin, codeine, dicumarol, indomethacin, isoniazid (INH), methotrexate, methyldopa, nafcillin, nalidixic acid, nitrofurantoin, oral contraceptives, oxacillin, phenothiazines, phenylbutazone, phenytoin, procainamide, propoxyphene, propranolol, quinidine, salicylates, tetracyclines, and verapamil.

Procedure and Patient Care

Before

Explain the procedure to the patient.

Tell the patient that no fasting is required.

During

• Collect a venous blood sample in a red-top tube and send it to the laboratory for analysis.

After

• Apply pressure or a pressure dressing to the venipuncture site.

• Assess the venipuncture site for bleeding. Patients with liver dysfunction often have prolonged clotting times.

Test Results and Clinical Significance

Significantly Increased Levels

Hepatitis

Hepatic necrosis

Hepatic ischemia

Moderately Increased Levels

Trauma to striated muscle

Mildly Increased Levels

Myositis,

Pancreatitis,

Myocardial infarction,

Infectious mononucleosis,

Shock:

Injury or disease affecting the liver, heart, or skeletal muscles will cause a release of this enzyme into the bloodstream, thus elevating serum ALT levels.

Related Tests

Aspartate Aminotransferase (AST) (p. 119). This is another enzyme existing predominantly in the liver.

Gamma-Glutamyl Transpeptidase (GGTP) (p. 246). This is another enzyme predominantly existing in the liver.

Alkaline Phosphatase (p. 47). This is another enzyme existing predominantly in the liver.

5′-Nucleotidase (p. 376). This is another enzyme existing predominantly in the liver.

Creatine Kinase (CK) (p. 186). This enzyme is used similarly to AST and exists predominantly in heart and skeletal muscle.

Lactic Dehydrogenase (LDH) (p. 329). This is an intracellular enzyme used to support the diagnosis of injury or disease involving the heart, liver, RBCs, kidneys, skeletal muscle, brain, and lungs.

Leucine Aminopeptidase (p. 337). This enzyme is specific to the hepatobiliary system. Diseases affecting that system will cause elevation of this enzyme.