04. Laboratory Diagnosis - Chemistry, Immunology, Serology


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Clinician's Pocket Reference > Chapter 4. Laboratory Diagnosis: Chemistry, Immunology, Serology >

Principles of Laboratory Testing

This chapter outlines commonly ordered blood chemistry, immunology, and serology tests and other common laboratory investigations. Normal values and a guide to the diagnosis of common abnormalities are provided. Additional tests are described in the following chapters: hematology, Chapter 5; urine studies, Chapter 6; microbiology, Chapter 7; and Blood Gases, Chapter 8. Increased or decreased values that are not clinically useful usually are not listed. Because each laboratory has its own set of normal reference intervals, the normal values given should be used only as a guide. Unless specified, values reflect normal levels in adults. The method of collection is included because laboratories have attempted to standardize collection methods; however, be aware that some labs may have other collection methods. Blood specimen tubes are listed in Chapter 13, Table 13 8.

Most laboratories offer AMA-recommended "panel" tests, whereby multiple determinations are performed on a single sample. Although labs may vary, common chemistry panels include the following:

  • AMA Electrolyte Panel: Sodium, potassium, chloride, CO2
  • AMA Basic Metabolic Panel: Calcium, CO2, chloride, creatinine, glucose, potassium, sodium, BUN
  • AMA Comprehensive Metabolic Panel: albumin, ALT, AST, total bilirubin, calcium, chloride, CO2, creatinine, glucose, alkaline phosphatase, potassium, total protein, sodium, BUN
  • AMA Renal Function Panel: Albumin, calcium, CO2, chloride, creatinine, glucose, phosphorus serum, potassium, sodium, BUN
  • AMA Hepatic Function Panel: Total protein, albumin, total bilirubin, direct bilirubin, alkaline phosphate, AST, ALT
  • AMA Lipid Panel: Cholesterol, HDL, LDL (calculated from cholesterol and hydroxycholesterol [HC]), triglycerides

Other Common Panel Tests

Chem-7 Panel/SMA-7: BUN, creatinine, electrolytes (Na, K, Cl, CO2), glucose
Health Screen-12/SMA-12: Albumin, alkaline phosphatase, AST (SGOT), bilirubin (total), calcium, cholesterol, creatinine, glucose, LDH, phosphate, protein (total), uric acid
Cardiac Enzymes: CK-MB (if total CK > 150 IU/L), troponin

Every reimbursable laboratory test has an associated CPT code used for billing transactions. The CPT (Current Procedural Terminology) system was developed by and is a registered trademark of the American Medical Association (AMA). CPT codes have been incorporated as the standard code set for Medicare and Medicaid reimbursement. They also are used in the Health Insurance Portability and Accountability Act (HIPAA) and have been adopted by private insurance carriers and managed care companies.

CPT codes are designated for services that are part of "contemporary medical practice and being performed by many physicians in clinical practice in multiple locations." Each of the codes consists of a five-digit number that is associated with a text descriptor (eg, 82565, Creatinine; blood).

To comply with government regulations as specified by the Centers for Medicare & Medicaid Services (CMS), clinical pathology laboratories require physicians who order tests to provide appropriate International Classification of Disease, Ninth Revision (ICD-9) diagnosis and procedure codes that in turn indicate which laboratory tests are reimbursable.

ACTH (Adrenocorticotropic Hormone, Corticotropin)

7 10 AM 10 50 pg/mL, PM results are lower Collection: Lavender top tube

Increased:

Addison disease (primary adrenal hypofunction), ectopic ACTH production (small [oat]-cell lung carcinoma, pancreatic islet cell tumors, thymic tumors, renal cell carcinoma, bronchial carcinoid), Cushing disease (pituitary adenoma), congenital adrenal hyperplasia (adrenogenital syndrome)

Decreased:

Adrenal adenoma or carcinoma, nodular adrenal hyperplasia, pituitary insufficiency, corticosteroid use

Albumin

Adult 3.5 5.0 g/dL, child 3.8 5.4 g/dL Collection: Tiger top tube; part of SMA-12

Decreased:

Malnutrition, overhydration, nephrotic syndrome, CF, multiple myeloma, Hodgkin disease, leukemia, metastatic cancer, protein-losing enteropathies, chronic glomerulonephritis, alcoholic cirrhosis, inflammatory bowel disease, collagen vascular diseases, hyperthyroidism

Aldosterone

Serum: Supine 3 10 ng/dL early AM, normal sodium intake (3 g sodium/d)

Upright 5 30 ng/dL; urinary 2 16 mcg/24 h Collection: Green or lavender top tube

Discontinue antihypertensives and diuretics 2 wk before test. Upright samples should be drawn after 2 h. Primarily used to screen hypertensive patients for possible Conn syndrome (adrenal adenoma producing excess aldosterone)

Increased:

Primary hyperaldosteronism, secondary hyperaldosteronism (CHF, sodium depletion, nephrotic syndrome, cirrhosis with ascites, others), upright posture

Decreased:

Adrenal insufficiency, panhypopituitarism, supine posture

Alkaline Phosphatase

Adult 25 160 IU/L, child 40 400 IU/L (method dependent) Collection: Tiger top tube; part of SMA-12

A fractionated alkaline phosphatase was formerly used to differentiate the origin of the enzyme in the bone from that in the liver. Replaced by GGT and 5'-nucleotidase measurements

Increased:

(Highest levels in biliary obstruction and infiltrative liver disease) Increased calcium deposition in bone (hyperparathyroidism), Paget disease, osteoblastic bone tumors (metastatic or osteogenic sarcoma), osteomalacia, rickets, PRG, childhood, healing fracture, liver disease, eg, biliary obstruction (masses, drug therapy), hyperthyroidism

Decreased:

Malnutrition, excess vitamin D ingestion, pernicious anemia, Wilson disease, hypothyroidism, zinc deficiency

Alpha-Fetoprotein (AFP)

< 6 mg/mL Third trimester of PRG maximum 550 mg/mL Collection: Tiger top tube

Increased:

Hepatoma (hepatocellular carcinoma), testicular tumor (embryonal carcinoma, malignant teratoma), neural tube defects (in mother's serum [spina bifida, anencephaly, myelomeningocele]), fetal death, multiple gestations, ataxia telangiectasia, some cases of benign hepatic disease (alcoholic cirrhosis, hepatitis, necrosis)

Decreased:

Trisomy 21 (Down syndrome) in maternal serum

ALT (Alanine Aminotransferase)

1 45 IU/L, higher in newborns Collection: Tiger top or red top tube

Increased:

Liver disease, liver metastasis, biliary obstruction, pancreatitis, liver congestion (ALT is more elevated than AST in viral hepatitis; AST elevated more than ALT in alcoholic hepatitis)

Ammonia

Adult 15 45 mcg/dL (9 27 mol/L) Collection: Green top tube, on ice, analyze immediately

Increased:

Liver failure, Reye syndrome, inborn errors of metabolism, healthy neonate (normalizes within 48 h of birth)

Amylase

10 130 U/L (method dependent) Collection: Tiger top or red top tube

Increased:

Acute pancreatitis, pancreatic duct obstruction (stones, stricture, tumor, sphincter spasm secondary to drugs), pancreatic pseudocyst or abscess, alcohol ingestion, mumps, parotiditis, renal disease, macroamylasemia, cholecystitis, peptic ulcer, intestinal obstruction, mesenteric thrombosis, aftermath of surgery

Decreased:

Pancreatic destruction (pancreatitis, cystic fibrosis), liver damage (hepatitis, cirrhosis), healthy infant in first year of life

Anti-CCP (Anti Cyclic Citrullinated Polypeptide Antibodies)

< 20 EU (ELISA units, assay dependent) Weak positive: 20 39 EU; moderate positive: 40 59 EU; strong positive: > 60 EU Collection: Tiger top or red top tube

Used with RA agglutinin test to diagnose RA. May be positive in early disease, differentiates positive RA test in other diseases

Increased:

RA (specificity > 95%, sensitivity 80%), rare false-positives with hepatitis and autoimmune thyroid disease

ASO Titer (Antistreptolysin O/Antistreptococcal O, Streptozyme)

< 200 IU/mL (Todd units) school-age children < 100 IU/mL preschool and adults Varies with lab Collection: Tiger top tube

Increased:

Streptococcal infection (pharyngitis, scarlet fever, rheumatic fever, poststreptococcal glomerulonephritis), RA, other collagen diseases

AST (Aspartate Aminotransferase)

7 42 IU/L Collection: Tiger top or red top tube; part of SMA-12

Generally parallels changes in ALT in liver disease

Increased:

AMI, liver disease, Reye syndrome, muscle trauma and injection, pancreatitis, intestinal injury or surgery, factitious increase (erythromycin, opiates), burns, cardiac catheterization, brain damage, renal infarction

Decreased:

Beriberi (vitamin B6 deficiency), severe diabetes with ketoacidosis, liver disease, chronic hemodialysis

Autoantibodies

Normal = negative Collection: Tiger top tube

Antinuclear Antibody (ANA, FANA)

Useful screening test in patients with symptoms suggesting collagen vascular disease, especially if titer is > 1:160. 5% of healthy people can have positive test.

Positive:

SLE, drug-induced lupus-like syndromes (eg, from procainamide, hydralazine, isoniazid), scleroderma, MCTD, RA, polymyositis, juvenile RA (5 20%). Low titers are also seen in diseases other than collagen vascular disease.

Specific Immunofluorescent ANA Patterns

Homogenous. Nonspecific, from antibodies to DNP and native double-stranded DNA. Seen in SLE and a variety of other diseases. Antihistone is consistent with drug-induced lupus.
Speckled. Pattern seen in many connective tissue disorders. From antibodies to ENA, including anti-RNP, anti-Sm, anti-PM-1, and anti-SS. Anti-RNP is positive in MCTD and SLE. Anti-Sm is highly specific for SLE (found in 30% of cases). Anti-SS-A and anti-SS-B are found in Sj gren syndrome and subacute cutaneous lupus.
Peripheral Rim Pattern. From antibodies to native double-stranded DNA and DNP. Seen in SLE
Nucleolar Pattern. From antibodies to nucleolar RNA. Positive in Sj gren syndrome and scleroderma

Anticentromere:

CREST syndrome, scleroderma, Raynaud disease

Anti-DNA (Anti double-stranded DNA):

SLE (but negative in drug-induced lupus), chronic active hepatitis, mononucleosis

Antimitochondrial:

Primary biliary cirrhosis, autoimmune diseases, eg, SLE

Antineutrophil Cytoplasmic (ANCA)

  • c-ANCA: Wegener granulomatosis (high titer = 1:80, highly predictive of Wegener granulomatosis)
  • p-ANCA: Polyarteritis nodosa and other forms of vasculitis, including Churg Strauss and microscopic polyarteritis
  • x- or atypical ANCA: Ulcerative colitis

Anti-CCP:

Rheumatoid arthritis

Anti-SCL 70:

Scleroderma

Antimicrosomal:

Hashimoto thyroiditis

Anti Smooth Muscle:

Low titers in a variety of illnesses; high titers (> 1:100) suggestive of chronic active hepatitis

Sj gren Syndrome Antibody (SS-A):

Sj gren syndrome, SLE, RA

Base Excess/Deficit

2 to +2 See Chapter 8, Acid-Base Disorders: Definitions

Beta-Hydroxybutyrate (BHB)

0.2 3.0 mg/dL Collection: Tiger top or red top tube

Replaces acetoacetate (acetone) in the diagnosis and management of DKA. BHB accounts for about 75% of the ketone bodies in blood; during periods of DKA, BHB increases more than the other two ketoacids (acetoacetate and acetone). BHB is used to assess the severity of DKA and to exclude hyperosmolar nonketotic diabetic coma. It is also useful in the detection of subclinical ketosis and in the management of DKA.

Positive: DKA, starvation, acute alcohol abuse

Bicarbonate ("Total Co2")

23 29 mmol/L See Carbon Dioxide

Bilirubin

Total, 0.3 1.0 mg/dL Direct, < 0.2 mg/dL Indirect, < 0.8 mg/dL Collection: Tiger top tube

Increased Total:

Hepatic damage (hepatitis, toxins, cirrhosis), biliary obstruction (stone or tumor), hemolysis, fasting

Increased Direct (Conjugated):

Note: Determination of direct bilirubin is usually unnecessary with total bilirubin levels < 1.2 mg/dL; biliary obstruction/cholestasis (gallstone, tumor, stricture), drug-induced cholestasis, Dubin Johnson and Rotor syndromes

Increased Indirect (Unconjugated):

Calculated as total minus direct bilirubin. Hemolytic jaundice caused by any type of hemolytic anemia (eg, transfusion reaction, sickle cell), Gilbert disease, physiologic jaundice of the newborn, Crigler Najjar syndrome

Bilirubin, Neonatal ("Baby Bilirubin")

Normal dependent on prematurity and age in days Critical values usually > 15 20 mg/dL in term infants Collection: Capillary tube

Increased:

Erythroblastosis fetalis, physiologic jaundice (may be due to breast feeding), resorption of hematoma or hemorrhage, obstructive jaundice, others

Blood Urea Nitrogen (BUN)

Birth 1 y: 4 16 mg/dL 1 40 y 5 20 mg/dL Gradual slight increase with age Collection: Tiger top tube

Less useful measure of GFR than creatinine because BUN is also related to protein metabolism

Increased:

Renal failure (including drug-induced from aminoglycosides, NSAIDs), prerenal azotemia (decreased renal perfusion secondary to CHF, shock, volume depletion), postrenal (obstruction), GI bleeding, stress, drugs (especially aminoglycosides)

Decreased:

Starvation, liver failure (hepatitis, drugs), PRG, infancy, nephrotic syndrome, overhydration

Bun/Creatinine Ratio (Bun/Cr)

Mean 10, range 6 20; calculation based on serum levels

Increased:

Prerenal azotemia (renal hypoperfusion can be due to decreased volume, CHF, cirrhosis/ascites, nephrosis), GI bleed (ratio often > 30), high-protein diet, sepsis/hypermetabolic state, ileal conduit, drugs (steroids, tetracycline)

Decreased:

Malnutrition, PRG, low-protein diet, ketoacidosis, hemodialysis, SIADH, drugs

C-Peptide, Insulin ("Connecting Peptide")

Fasting, 1 5 mg/mL (method dependent) Collection: Tiger top or red top tube

Used to differentiate endogenous insulin from exogenous and production/administration; liberated when proinsulin split to insulin; levels reflect endogenous insulin production

Increased:

Insulinoma, sulfonylurea ingestion

Decreased:

Type 1 diabetes (decreased endogenous insulin), insulin administration (factitious or therapeutic), factitious hypoglycemia

C-Reactive Protein (CRP)

Normal < 0.8 mg/dL Collection: Tiger top or red top tube

A nonspecific screen for infectious and inflammatory diseases, correlates with ESR. In the first 24 h, however, ESR may be normal and CRP elevated. CRP returns to normal more quickly than ESR in response to therapy.

Increased:

Bacterial infections, inflammatory conditions (acute rheumatic fever, acute RA, MI, unstable angina, transplant rejection, embolus, inflammatory bowel disease), last half of PRG, oral contraceptives, some malignant diseases

CA 15-3

< 35 U/mL Collection: Tiger top or red top tube

Used to detect breast cancer recurrence and monitor therapy. Levels related to stage of disease

Increased:

Progressive breast cancer, benign breast disease and liver disease

Decreased:

Response to therapy (25% change considered significant)

CA 19-9

< 37 U/mL Collection: Tiger top tube

Primarily used to determine resectability of pancreatic cancer (ie, > 1000 U/mL 95% unresectable)

Increased:

GI cancers, eg, pancreas, stomach, liver, colorectal, hepatobiliary, some cases of lung and prostate, pancreatitis

CA-125

< 35 U/mL Collection: Tiger top tube

Not useful screening test for ovarian cancer; best used in conjunction with ultrasonography and physical exam. Rising levels after resection predictive of recurrence

Increased:

Ovarian, endometrial, and colon cancer; endometriosis; inflammatory bowel disease; PID; PRG; breast lesions; benign abdominal masses (teratomas)

Calcitonin (Thyrocalcitonin)

< 19 pg/mL (method dependent) Collection: Tiger top tube

Increased: Medullary carcinoma of the thyroid, C-cell hyperplasia (precursor of medullary carcinoma), small (oat)-cell carcinoma of the lung, newborn state, PRG, chronic renal insufficiency, Zollinger Ellison syndrome, pernicious anemia

Calcium, Serum

Infants younger than 1 mo: 7 11.5 mg/dL 1 mo 1 y: 8.6 11.2 mg/dL

> 1 y and adults: 8.2 10.2 mg/dL Ionized: 4.75 5.2 mg/dL Collection: Tiger top or red top tube; ionized green or red top tube

For interpretation of total calcium, albumin must be known. If albumin is not normal, corrected calcium is estimated with the following formula. Values for ionized calcium need no special corrections.

Increased:

(Note: Levels > 12 mg/dL may lead to coma and death.) Primary hyperparathyroidism, PTH-secreting tumors, vitamin D excess, metastatic bone tumors, osteoporosis, immobilization, milk alkali syndrome, Paget disease, idiopathic hypercalcemia of infants, infantile hypophosphatasia, thiazide diuretics, chronic renal failure, sarcoidosis, multiple myeloma

Decreased:

(Levels < 7 mg/dL may lead to tetany and death.) Hypoparathyroidism (surgical, idiopathic), pseudohypoparathyroidism, insufficient vitamin D, calcium and phosphorus ingestion (PRG, osteomalacia, rickets), hypomagnesemia, RTA, hypoalbuminemia (cachexia, nephrotic syndrome, CF), chronic renal failure (phosphate retention), acute pancreatitis, factitious condition (low protein and albumin)

Carbon Dioxide ("Total Co2" or Bicarbonate)

Adult 23 29 mmol/L, child 20 28 mmol/L (See Chapter 8 for PCO2 values) Collection: Tiger top tube; do not expose sample to air

Increased:

Compensation for respiratory acidosis (emphysema) and metabolic alkalosis (severe vomiting, primary aldosteronism, volume contraction, Bartter syndrome)

Decreased:

Compensation for respiratory alkalosis and metabolic acidosis (starvation, DKA, lactic acidosis, alcoholic ketoacidosis, toxins [methanol, ethylene glycol, paraldehyde], severe diarrhea, renal failure, drugs [salicylates, acetazolamide], dehydration, adrenal insufficiency)

Carboxyhemoglobin (Carbon Monoxide)

Nonsmoker < 2% Smoker < 9% Toxic > 15% Collection: Gray or lavender top tube; confirm with lab

Increased:

Smokers, smoke inhalation, automobile exhaust inhalation, healthy newborns

Carcinoembryonic Antigen (CEA)

Nonsmoker < 3.0 ng/mL Smoker < 5.0 ng/mL Collection: Tiger top or red top tube

Not a cancer screening test; used to monitor response to treatment and tumor recurrence in GI tract adenocarcinoma

Increased:

Carcinoma (colon, pancreas, lung, stomach), smokers, nonneoplastic liver disease, Crohn disease, ulcerative colitis

Catecholamines, Fractionated Serum

Collection: Green or lavender tube; check with lab

Values vary and depend on the lab and method of assay used. Normal levels shown here are based on an HPLC technique. Patient must be supine in a nonstimulating environment with IV access to obtain sample.

CatecholaminePlasma (Supine) Levels
Norepinephrine70 750 pg/mL (SI: 414 435 pmol/L)
Epinephrine0 100 pg/mL (SI: 0 546 pmol/L)
Dopamine< 30 pg/mL (SI: 196 pmol/L)

Increased:

Pheochromocytoma, neural crest tumors (neuroblastoma); with extraadrenal pheochromocytoma norepinephrine may be markedly elevated compared with epinephrine

Chloride, Serum

97 107 mEq/L Collection: Tiger top tube

Included with electrolytes in most metabolic panels

Increased:

Diarrhea, RTA, mineralocorticoid deficiency, hyperalimentation, medications (acetazolamide, ammonium chloride)

Decreased:

Vomiting, DM with ketoacidosis, mineralocorticoid excess, renal disease with sodium loss

Cholesterol

Total Normal, Table 4 1; see also Lipid Profile, and Table 4 2 Collection: Tiger top or red top tube

Table 4 1 National Cholesterol Education Program New Clinical Guidelines for Cholesterol Testing and Management


Step 1: Complete lipoprotein profile (mg/dL) after 9- to 12-h fast 
<70Low LDL
70 99Optimal
100 129Near optimal/above optimal
130 159Borderline high
160 189High
190Very high
Step 2: Identify presence of clinical atherosclerotic disease that confers high risk for CHD events (CHD risk equivalent): 
  Clinical CHD or symmptomatic CAD or peripheral arterial disease, TIA, AAA, or diabetes.
Step 3: Determine presence of major risk factors (other than LDL): 
  Cigarette smoking; HTN (BP 140/90 mm Hg or on BP medications); HDL <40 mg/dL (if 60 mg/dL remove one risk factor from count); family history of premature CHD (CHD in male relative <55 y; CHD in female relative <65 y); age (men 45 y; women 55 y).
Step 4: If 2+ risk factors (other than LDL) are present without CHD or CHD risk equivalent, assess 10-y (short-term) CHD risk (see Framingham tables @ http://www.nhlbi.nih.gov/guidelines/cholesterol/risk_tbl.htm). 
  Three levels of 10-y risk: >20%, 10 20%, <10%
Step 5: Establish LDL goal of therapy, determine need for TLC, determine level for drug consideration. 
Risk Category LDL Goal (mg/dL) LDL Level to Initiate TLC (mg/dL) LDL Level to Consider Drug Therapy (mg/dL) 
aVery high risk (CHD or CHD equivalents) (10-yr risk > 20%)
 
<70>70>70a
 
High risk (CHD or CHD risk equivalents) (10-yr risk >20%)<100>100>100
Moderately high risk 2+ risk factors (10-yr risk 10 20%)<100100130
Moderate risk 2+ risk factors (10-yr risk < 10%)<130130160
bLow risk 0 1 risk factors (10-yr risk < 10%)
 
<160160190
Step 6: Initiate TLC if LDL is above goal. 
  TLC diet: Saturated fat <7% of calories, cholesterol <200 mg/d, increased viscous (soluble) fiber (10 25 g/d) and plant stanols/sterols (2 g/d), weight management, and increased physical activity.
Step 7: Consider adding drug therapy if LDL exceeds levels shown in Step 5 table: 
  HMG-CoA reductase inhibitors (statins), bile acid sequestrants, nicotinic acid.
Step 8: Identify metabolic syndrome and treat, if present, after 3 mo of TLC. Metabolic syndrome present if any 3 of the following present: 
Risk Factor Defining Level 
Abdominal obesityWaist circumferencea
 
  Men>102 cm (>40 in)
  Women>88 cm (>35 in)
Triglycerides150 mg/dL
HDL cholesterol 
  Men<40 mg/dL
  Women<50 mg/dL
BP130/85 mm Hg
Fasting glucose110 mg/dL

aOverweight and obesity are associated with insulin resistance and the metabolic syndrome.

  Manage metabolic syndrome: control underlying causes (overweight/obesity and physical inactivity); control lipid and nonlipid risk factors if they persist despite these lifestyle therapies; manage HTN, aspirin for CHD prevention; control elevated triglycerides and/or low HDL (as shown in Step 9).

Step 9: Manage elevated triglycerides (150 mg/dL): Primary aim of therapy is to reach LDL goal; intensify weight management, increase physical activity; if triglycerides 200 mg/dL after LDL goal is reached, set secondary goal for non-HDL cholesterol (total HDL) 30 mg/dL higher than LDL goal.

Classification of Serum Triglycerides (mg/dL) 
<150Normal
150 199Borderline high
200 499High
500Very high
Comparison of LDL Cholesterol and Non-HDL Cholesterol Goals for Three Risk Categories 
Risk Category LDL Goal (mg/dL) Non-HDL Goal (mg/dL) 

CHD and CHD risk equivalent (10-y risk for CHD >20%)

<100

<130

Multiple (2+) risk factors and 10-y risk 20%

<130

<160

0 1 risk factor

<160

<190

If triglycerides 200 499 mg/dL after LDL goal is reached, consider adding drug if needed to reach non-HDL goal: Intensify therapy with LDL-lowering drug, or add nicotinic acid or fibrate to further lower VLDL.

If triglycerides 500 mg/dL, first lower triglycerides to prevent pancreatitis: Very-low-fat diet (15% of calories from fat), weight management and physical activity, fibrate or nicotinic acid, when triglycerides <500 mg/dL, turn to LDL-lowering therapy.

Management of low HDL cholesterol (<40 mg/dL): First reach LDL goal, then weight management and increase physical activity; if triglycerides 200 499 mg/dL, achieve non-HDL goal. If triglycerides <200 mg/dL (isolated low HDL) in CHD or CHD equivalent, consider nicotinic acid or fibrate.


aSome use LDL-lowering drugs in this category if an LDL cholesterol <70 or 100 mg/dL cannot be achieved by lifestyle changes. Others use drugs that modify triglycerides and HDL, eg, nicotinic acid or fibrate.

bAlmost all people with 0 1 risk factor have a 10-y risk <10%, thus 10-y risk assessment in people with 0 1 risk factor is not necessary.

LDL = low-density lipoprotein; HDL = high-density lipoprotein; CHD = coronary heart disease; CAD = carotid artery disease; AAA = abdominal aortic aneurysm; HTN = hypertension; BP = blood pressure; TLC = therapeutic lifestyle changes; HMG-CoA = hydroxymethylglutaryl coenzyme A.

Based on the Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel or ATP III) (http://www.nhlbi.nih.gov/guidelines/cholesterol) accessed March, 10, 2006, U.S. Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD.

Table 4 2 Lipoproteins


Frederickson Classification SystemType I (Rare)Type IIa (Common)Type IIb (Common)Type III (Uncommon)Type IV (Uncommon)Type V (Uncommon)
CholesterolN or slightly Very Very Very N or slightly
LDLNNN
HDLN or N or N or N or N or N or
TriglyceridesVery NVery Very
Increased lipoproteinsChylomicronsLDLLDL, VLDLLDLVLDLVLDL and chylomicrons
Atherogenesis riskNo increaseVery No increaseNo increase

Increased:

Idiopathic hypercholesterolemia, biliary obstruction, nephrosis, hypothyroidism, pancreatic disease (diabetes), PRG, oral contraceptives, hyperlipoproteinemia (types IIb, III, V)

Decreased:

Liver disease (eg, hepatitis), hyperthyroidism, malnutrition (cancer, starvation), chronic anemia, steroid therapy, lipoproteinemia, AMI

High-Density Lipoprotein Cholesterol (HDL, HDL-C)

Fasting men: 30 70 mg/dL Women: 30 90 mg/dL

HDL-C: Best correlation with the development of CAD; decreased HDL-C in men leads to increased risk. Levels < 40 mg/dL associated with increased risk of CAD. Levels > 60 mg/dL associated with decreased risk of CAD

Increased:

Estrogen (menstruating women), regular exercise, small ethanol intake, medications (nicotinic acid, gemfibrozil, others)

Decreased:

Men, smoking, uremia, obesity, diabetes, liver disease, Tangier disease

Low-Density Lipoprotein Cholesterol (LDL, LDL-C)

50 190 mg/dL

Elevated levels correlate with CAD risk.

Increased:

Excess dietary saturated fats, hyperlipoproteinemia, biliary cirrhosis, endocrine disease (diabetes, hypothyroidism)

Decreased:

Malabsorption, severe liver disease, abetalipoproteinemia

Clostridium Difficile Toxin Assay, Fecal

Normal = negative

Positive:

> 90% of cases of pseudomembranous colitis; 30 40% of antibiotic-associated colitis, and 6 10% of antibiotic-associated diarrhea. False-positive in some healthy adults and neonates

Cold Agglutinins

< 1:32 Collection: Lavender or blue top tube

Most frequently used to screen for atypical pneumonia

Increased:

Atypical pneumonia (mycoplasmal pneumonia), other viral infections (especially mononucleosis, measles, mumps), cirrhosis, parasitic infections, Waldenstr m macroglobulinemia, lymphoma and leukemia, multiple myeloma

Complement

Collection: Tiger or red top tube

Complement describes a series of sequentially reacting serum proteins that participate in pathogenic processes and cause inflammatory injury.

Complement C3

85 155 mg/dL (method dependent)

Decreased level suggests activation of the classical or alternative pathway or both.

Increased:

RA (variable finding), rheumatic fever, various neoplasms (GI, prostate, others), acute viral hepatitis, MI, PRG, amyloidosis

Decreased:

SLE, glomerulonephritis (poststreptococcal and membranoproliferative), sepsis, SBE, chronic active hepatitis, malnutrition, DIC, gram-negative sepsis

Complement C4

20 50 mg/dL (method dependent)

Increased:

RA (variable finding), neoplasia (GI, lung, others)

Decreased:

SLE, chronic active hepatitis, cirrhosis, glomerulonephritis, hereditary angioedema (test of choice)

Complement CH50 (Total)

33 61 mg/mL (method dependent)

Tests of complement deficiency in the classical pathway

Increased:

Acute-phase reactants (eg, tissue injury, infections)

Decreased:

Hereditary complement deficiencies

Cortisol, Serum

8 AM, 5.0 23.0 mg/dL 4 PM, 3.0 15.0 mg/dL (method dependent) Collection: Green or red top tube

Increased:

Adrenal adenoma, adrenal carcinoma, Cushing disease, nonpituitary ACTH-producing tumor, steroid therapy, oral contraceptives

Decreased:

Primary adrenal insufficiency (Addison disease), congenital adrenal hyperplasia, Waterhouse Friderichsen syndrome, ACTH deficiency

Cortrosyn Stimulation Test, 1-Hour ("Short")

Collection: Red top tube

Used to diagnose adrenal insufficiency. Cortrosyn, an ACTH analogue, is given (0.25 mg IM or IV in adults). Blood is collected for serum cortisol measurement 60 min later. Consider obtaining informed consent for this chemically invasive procedure.

Normal Response:

Serum cortisol increase > 20 mcg/dL 60 min after Cortrosyn is given.

Abnormal Response:

Serum cortisol < 20 mcg/dL 60 min after Cortrosyn administration; primary adrenal insufficiency (Addison disease), pituitary insufficiency (insufficient stimulation of the adrenal glands by pituitary ACTH), or chronic suppression by exogenous steroids

Creatine Kinase, Total (CK)

25 145 mU/mL Collection: Tiger top tube

Used in suspected MI or muscle diseases. Heart, skeletal muscle, and brain have high levels.

Increased:

Muscle damage (AMI, myocarditis, muscular dystrophy, muscle trauma [including injections], aftermath of surgery), brain infarction, defibrillation, cardiac catheterization and surgery, rhabdomyolysis, polymyositis, hypothyroidism

CPK Isoenzymes

MB:

(Normal < 6%, heart origin) increased in AMI (begins in 2 12 h, peaks at 12 40 h, returns to normal in 24 72 h); troponin is marker of choice for AMI; pericarditis with myocarditis, rhabdomyolysis, crush injury, Duchenne muscular dystrophy, polymyositis, malignant hyperthermia, cardiac surgery

MM:

(Normal 94 100%, skeletal muscle origin) increased in crush injury, malignant hyperthermia, seizures, IM injections

Bb:

(Normal 0%, brain origin) brain injury (CVA, trauma), metastatic neoplasms (eg, prostate), malignant hyperthermia, colonic infarction

Creatinine, Serum (SCr)

Men: < 1.2 mg/dL Women: < 1.1 mg/dL Children 0.5 0.8 mg/dL Collection: Tiger or red top tube

A clinically useful estimate of GFR. In general, SCr doubles with each 50% reduction in GFR. Creatine clearance based on urinary collection is considered the most accurate method (see Chapter 6).

Increased:

Renal failure (prerenal, renal, or postrenal obstruction or medication-induced [aminoglycosides, NSAIDs, others]), gigantism, acromegaly, ingestion of red meat, false-positive with DKA

Decreased:

PRG, decreased muscle mass, severe liver disease

Cryoglobulins (Cryocrit)

< 0.4% (negative if qualitative) Collection: prewarmed red top tube; contact lab before collecting; transport at body temperature

Cryoglobulins are abnormal proteins that precipitate out of serum at low temperatures. Cryocrit (quantitative) is preferred over qualitative method. Request analysis of positive results for immunoglobulin class and light-chain type.

Monoclonal:

Multiple myeloma, Waldenstr m macroglobulinemia, lymphoma, CLL

Mixed Polyclonal or Mixed Monoclonal:

Infectious diseases (viral, bacterial, parasitic), eg, SBE or malaria; SLE; RA; essential cryoglobulinemia; lymphoproliferative diseases; sarcoidosis; chronic liver disease (cirrhosis)

Cytomegalovirus (CMV) Antibodies

IgM < 1:8, IgG < 1:16 Collection: Tiger top tube

Used in neonates (CMV is the most common intrauterine infection), posttransfusion CMV infection, screening of organ donors and recipients. Most adults have detectable titers. In neonates, CMV Ab titer may be passive from mother. CMV PCR viral load may be more useful in neonates and in diagnosing active CMV infection in adults.

Increased:

Serial measurements 10 14 d apart with a 4x increase in titers or a single IgM > 1:8 suggest acute infection. Universally increased titers in AIDS. IgM most useful in neonatal infections, but many false-positives; less likely to be positive owing to maternal CMV antibodies. With IgM half-life of 1 month, takes 2 3 months to see drop.

D-Dimer

(See also Chapter 5, Fibrin D-Dimers.)

Negative Collection: Sky blue top tube

D-Dimers are proteins released with fibrinolytic breakdown of fibrin; used to evaluate suspected DVT and PE; level returns to normal if clot stabilized (ie, treated with heparin) and not undergoing any further fibrin deposition or plasmin activation

Increased:

DVT, PE, MI, CVA, sickle cell crisis, cancer, renal failure, CHF, life-threatening infections

Dehydroepiandrosterone (DHEA)

Men: 2.0 13.0 ng/mL Premenopausal women: 1.0 11.0 ng/mL Postmenopausal: 0.5 5.0 ng/mL (method dependent) Collection: Red top tube

Increased:

Anovulation, polycystic ovaries, adrenal hyperplasia, adrenal tumors

Decreased:

Menopause

Dehydroepiandrosterone Sulfate (DHEAS)

Men: 30 300 mcg/dL Women: 40 200 mcg/dL Collection: Tiger top tube

Increased:

Hyperprolactinemia, adrenal hyperplasia, adrenal tumor, polycystic ovaries, lipoid ovarian tumors

Decreased:

Menopause

Dexamethasone Suppression Test

Used to confirm or exclude the diagnosis of Cushing syndrome (increased serum cortisol)

Overnight Test:

The "rapid" screening version. Patient takes 1 mg of dexamethasone PO at 11 PM and fasts overnight; draw red top tube at 8 AM for serum cortisol. Consider sleeping pill hs for anxious or stressed patients. If 8 AM cortisol is < 3 mcg/dL, the pituitary adrenal axis suppresses normally, which excludes Cushing syndrome. An 8 AM serum cortisol 3 mcg/dL is abnormal. Result should be interpreted cautiously; many false-positives (obesity, major anxiety/depression, severe stress, exogenous estrogen or anticonvulsant therapy, pregnancy, alcoholism). Use 24-h urine collection for urinary free cortisol and creatinine as a screen for Cushing syndrome in these patients (see Chapter 6).

Two-Day Low-Dose Dexamethasone Suppression Test:

Day 1, draw a baseline serum cortisol (red top tube) and collect 24-h urine for free cortisol and creatinine. At 6 AM day 2, give 0.5 mg of dexamethasone PO q6h x 8 doses. On day 3, collect another 24-h urine for urinary free cortisol excretion and creatinine. On days 3 and 4 draw red top tube at 8 AM. Normal: suppression (cortisol < 5 mcg/dL) by day 4 or urinary free cortisol < 10% of baseline; this result excludes Cushing syndrome. Failure to suppress serum cortisol and/or urinary free cortisol increases the likelihood of Cushing syndrome; false-positives with rapid dexamethasone metabolizers, anticonvulsant therapy, severe depression or stress, alcoholism.

High-Dose Dexamethasone Suppression Test:

Similar to the low-dose test except that 2 mg of dexamethasone is given PO q6h x 8 doses; serum cortisol is not drawn. If urinary free cortisol < 90% of baseline, suppressible pituitary adenoma is likely, otherwise a nonpituitary cause of Cushing syndrome should be sought.

Erythropoietin (EPO)

4 16 mU/mL Collection: Tiger top or red top tube

EPO is a renal hormone that stimulates RBC production.

Increased:

PRG, secondary polycythemia (eg, high altitude, COPD), tumors (renal cell carcinoma, cerebellar hemangioblastoma, hepatoma, others), PCKD, anemias with bone marrow unresponsiveness (eg, aplastic anemia, iron deficiency)

Decreased:

Bilateral nephrectomy, anemia of chronic disease (ie, renal failure, nephrotic syndrome), primary polycythemia (Note: Determination of EPO levels before administration of recombinant EPO for renal failure is not usually necessary.)

Estradiol, Serum

Collection: Tiger top or red top tube

Serial measurements useful in evaluation of fetal well-being, especially in high-risk PRG; amenorrhea; and gynecomastia in male patients

Female Patients

Normal Value

Follicular phase

25 75 pg/mL

Midcycle peak

200 600 pg/mL

Luteal phase

100 300 pg/mL

Pregnancy

  1st trimester

1 5 ng/mL

  2nd trimester

5 15 ng/mL

  3rd trimester

10 40 ng/mL

Postmenopause

5 25 pg/mL

Oral contraceptives

<50 pg/mL

Male Patients

Prepubertal

2 8 pg/mL

Adult

10 60 pg/mL


Estrogen/Progesterone Receptors

Determined with fresh surgical breast cancer specimens. Presence of the receptors (ER-positive, PR-positive) is associated with improved outcome and increased likelihood of responding to endocrine therapy (eg, tamoxifen); 50 75% of breast cancers are estrogen-receptor-positive.

Ethanol (Blood Alcohol)

0 mg/dL Collection: Tiger top or red top tube; do not use alcohol to clean venipuncture site, use povidone-iodine

Physiologic changes can vary with degree of alcohol tolerance of an individual.

  • < 50 mg/dL: Limited muscular incoordination
  • 50 100 mg/dL: Pronounced incoordination
  • 100 150 mg/dL: Mood and personality changes; intoxication over the legal limit in most states
  • 150 400 mg/dL: Nausea, vomiting, marked ataxia, amnesia, dysarthria
  • > 400 mg/dL: Coma, respiratory insufficiency and death

Fecal Fat

Quantitative 2 6 g/d on an 80 100 g/d fat diet 72-h collection time (refrigerate sample) Random sample Sudan III or IV stain, < 60 droplets fat/hpf

Aids in diagnosis of malabsorption, steatorrhea. Most fat normally absorbed in small bowel

Increased:

Pancreatic dysfunction (chronic pancreatitis, CF, Shwachman Diamond syndrome), diarrhea with or without fat malabsorption (any diarrhea state alters fat absorption), regional enteritis (Crohn disease), celiac disease

Fecal Occult Blood Test (FOBT)

Normal: Negative Collection: Diet free of exogenous peroxidases (fish, horseradish, turnips), no vitamin C or medicines that irritate GI tract (eg, NSAIDS). Patient collects 2 3 consecutive stool specimens and uses a wooden stick to place sample on assay card. Rectal exam sample may also be used.

Annual FOBT reduces colorectal cancer deaths 15 33%. Test based on detecting stool peroxidase activity. Hemoccult II test entails use of guaiac-impregnated paper and developer to detect oxidation of a colorless indicator to a colored (blue) one in the presence of hemoglobin pseudoperoxidase. More sensitive assays are immunochemical tests such as HemSelect (HS) and FlexSure (FS) in which anti-human hemoglobin antibodies are used to detect stool human hemoglobin.

Positive:

Colon or rectal polyps or cancer, hemorrhoids, anal fissures, esophageal or gastric cancer, peptic ulcers, ulcerative colitis, Crohn disease, GERD, esophageal varices, vascular ectasia

False-Positive:

Recent dental procedure with bleeding gums, eating red meat within 3 days of test, fish, turnips, horseradish, or drugs such as colchicines and oxidizing drugs (eg, iodine and boric acid)

False-Negative:

High doses of vitamin C

Ferritin

Men: 20 500 ng/mL Women: 20 200 ng/mL Collection: Tiger top or red tube

Ferritin is the major storage protein for iron and is most useful in anemia work-up; used to differentiate iron deficiency from anemia of chronic disease. An acute phase reactant

Increased:

Iron excess (hemochromatosis, hemosiderosis), porphyria, sideroblastic anemia, malignancies (leukemia, Hodgkin disease), type 2 DM, postpartum state, chronic inflammation (eg, RA), hyperthyroidism

Decreased:

Iron deficiency (earliest and most sensitive test before RBC morphologic change)

Folate (Folic Acid)

Serum > 3.5 mcg/L RBC folate 270 600 ng/mL Collection: Lavender top tube

Serum folate fluctuates with diet. RBC levels are indicative of tissue stores. Vitamin B12 deficiency can impede the ability of RBCs to take up folate despite normal serum folate level.

Increased:

Folic acid administration

Decreased:

Malnutrition/malabsorption (folic acid deficiency), massive cellular growth (cancer) or cell turnover, ongoing hemolysis, medications (trimethoprim, some anticonvulsants, oral contraceptives), vitamin B12 deficiency (low RBC levels), PRG

Follicle-Stimulating Hormone (FSH)

Men: < 13 IU/L Women: nonmidcycle < 20 IU/L, midcycle surge < 40 IU/L; midcycle peak should be 2 x basal level Postmenopausal 40 160 IU/L Collection: Tiger top or red top tube

Used in work-up of impotence, male infertility, and female amenorrhea

Increased:

(Hypergonadotropic > 40 IU/L) postmenopausal, surgical/chemical castration, gonadal failure, gonadotropin-secreting pituitary adenoma

Decreased:

(Hypogonadotropic < 5 IU/L) prepubertal, hypothalamic and pituitary dysfunction, PRG

FTA-ABS (Fluorescent Treponemal Antibody Absorbed)

Normal = nonreactive Collection: Tiger top tube

Test of choice to confirm syphilis after positive RPR. Can be negative in early primary syphilis and remain positive after treatment

Positive:

Syphilis, other treponemal infections (yaws, pinta, bejel); false-positive (Lyme disease, leprosy, malaria), PRG, other diseases with increased ANA or immunoglobulins

Fungal Serologies

Negative or no bands identified Collection: Tiger top or red top tube

A screen for fungal antibodies; used to detect antibodies to Histoplasma capsulatum, Blastomyces dermatitidis, Aspergillus species, Candida species, and Coccidioides immitis. Serum clinical utility limited; best for testing CSF for Coccidioides

Gastrin, Serum

Fasting < 100 pg/mL Postprandial 95 140 pg/mL Collection: Tiger top tube, immediately transport to lab and freeze serum

Make sure patient is not taking H2 blockers or antacids.

Increased:

Zollinger Ellison syndrome, medications (antacids, H2 blockers, proton-pump inhibitors [PPIs]) pyloric stenosis, pernicious anemia, atrophic gastritis, ulcerative colitis, renal insufficiency, steroid and calcium administration

Decreased:

Vagotomy and antrectomy

Glucose

Fasting, < 110 mg/dL Collection: Tiger top or red top tube

American Diabetes Association Diagnostic Criterion for Diabetes: normal fasting < 100 mg/dL, impaired fasting 100 125 mg/dL on more than one occasion or any random level > 200 mg/dL when associated with symptoms such as polyuria, polydipsia, polyphagia, and weight loss.

Increased:

DM (types 1 and 2), Cushing syndrome, acromegaly, increased epinephrine (eg, injection, pheochromocytoma, stress, burns), acute and chronic pancreatitis, ACTH administration, spurious cause (sample from site above IV containing dextrose), advanced age, pancreatic glucagonoma, drugs (glucocorticoids, thiazide diuretics)

Decreased:

Pancreatic disorders (islet cell tumors), extrapancreatic tumors (carcinoma of adrenal gland, stomach), hepatic disease (hepatitis, cirrhosis, tumors), endocrine disorders (early diabetes, hypothyroidism, hypopituitarism), functional disorders (after gastrectomy), pediatric problems (prematurity, infant of diabetic mother, ketotic hypoglycemia, enzyme diseases), exogenous insulin, oral hypoglycemic agents, malnutrition, sepsis

Glucose Tolerance Test (GTT), Oral (OGTT)

A fasting glucose level 126 mg/dL or a random glucose > 200 mg/dL (11.1 mmol/L) is the threshold for diagnosis of DM; confirmation on a subsequent day precludes the need for glucose challenge. GTT is not necessary for diagnosis of DM and may be useful in gestational DM. Unreliable in the presence of severe infection, prolonged fasting, or after insulin injection. After an 8 12 h overnight fast (water only), a fasting blood glucose sample is drawn, and the patient ingests a 75-g oral glucose load, usually by drinking "glucola" (100 g for gestational DM screening, 1.75 mg/kg ideal body weight in children up to 75 g). Glucose drawn 30 min, 1, 2 and 3 h after glucose load.

Interpretation of GTT

Normal Glucose Tolerance:

Glucose < 140 mg/dL 2 h after glucose load

Impaired fasting glucose: Fasting glucose > 110 mg/dL and < 126 mg/dL risk factor for future diabetes

Impaired Glucose Tolerance:

Glucose 140 199 mg/dL 2 h after glucose load

Diabetes: Glucose > 200 mg/dL 2 h after glucose load

Gestational Diabetes:

OTT usually done at about 28 wk with any two of the following glucose levels diagnostic: fasting > 105 mg/dL, 1-h > 190 mg/dL, 2-h > 165 mg/dL, or 3-h > 145 mg/dL

Glutamyl Transferase (GGT)

Men: 9 50 U/L Women: 8 40 U/L Collection: Tiger top tube

Parallels changes in serum alkaline phosphatase and 5'-nucleotidase in liver disease. Sensitive indicator of alcoholic liver disease

Increased:

Liver disease (hepatitis, cirrhosis, obstructive jaundice), pancreatitis

Glycohemoglobin (GHB, Glycated Hemoglobin, Glycohemoglobin, HbA1c, HbA1 Hemoglobin A1c, Glycosylated Hemoglobin)

Interpretation: Nondiabetic < 6%, near normal 6 7% Excellent glucose control < 7% Good control 7 8% Fair control 8 9% Poor control > 10% Collection: Lavender top tube

Mean plasma glucose is equal to (HbA1c x 35.6) 77.3. Useful in long-term monitoring control of blood sugar in diabetic patients; reflects levels over preceding 3 4 mo; not used to diagnose DM

Increased:

DM (uncontrolled), lead intoxication

Decreased:

Chronic renal failure, hemolytic anemia, PRG, chronic blood loss

Haptoglobin

40 180 mg/dL Collection: Tiger top or red top tube

Increased:

Obstructive liver disease, any cause of increased ESR (inflammation, collagen vascular diseases)

Decreased:

Any type of hemolysis (eg, transfusion reaction), liver disease, anemia, oral contraceptives, childhood and infancy

Helicobacter Pylori Antibody Titers

IgG < 0.17 = negative

Most patients with gastritis and ulcer disease have chronic H. pylori infection that should be controlled. Positive in 35 50% of patients without symptoms (increases with age). Use in dyspepsia controversial. Methods to test for H. pylori: noninvasive (serology, 13C or 14C urea breath test one of the most accurate noninvasive tests currently available, fecal assay [see Helicobacter pylori Antigen, Feces]) and invasive ("gold standard" gastric mucosal biopsy and Campylobacter-like organism test). The IgG subclass is found in all patient populations; occasionally only IgA antibodies can be detected. Serology most useful in newly diagnosed H. pylori infection or monitoring response to therapy. IgG levels decrease slowly after treatment and can remain elevated after infection clears.

Positive:

Active or recent H. pylori infection, some asymptomatic carriers

Helicobacter Pylori Antigen, Feces

Collection: 5 g of stool in a screw-capped, plastic container. Submit promptly to lab. Watery, diarrheal specimens or stool in transport media, swabs, or preservatives cannot be tested.

Uses: diagnosis of H. pylori and monitoring H. pylori clearing after therapy. Persons without symptoms should not be tested.

Positive:

H. pylori antigen present in the stool

Negative:

Absence of detectable antigen; does not exclude the possibility of infection by H. pylori

Hepatitis Testing

Recommended hepatitis panel tests based on clinical settings are shown in Table 4 3, and pattern interpretation in Table 4 4. Profile patterns of hepatitis A and B are shown in Figures 4 1 and 4 2.

Table 4 3 Hepatitis Panel Testing to Guide the Ordering of Hepatitis Profiles for Given Clinical Settings


Clinical SettingTestPurpose
Screening Tests 
PregnancyHBsAga
 
All expectant mothers should be screened during third trimester
High-risk patients on admission (homosexuals, dialysis patients)HBsAgTo screen for chronic or active infection
Percutaneous inoculation  
  DonorHBsAgTo test patient's blood (esp. dialysis and HIV patients) for infectivity with hepatitis B and C if a health care worker is exposed
Anti-HBc IgM
Anti-Hep C
  VictimHBsAgTo test exposed health care worker for immunity or chronic infection
Anti-HBc
Anti-Hep C
Pre-HBV vaccineAnti-HBcTo determine if a high-risk individual is infected or has antibodies to HBV
Anti-HBs
Screening blood HBsAgUsed by blood banks to screen donors for hepatitis B and C
Anti-HBc
Anti-Hep C
Diagnostic Tests 
Differential diagnosis of acute jaundice, hepatitis, or fulminant liver failureHBsAgTo differentiate HBV, HAV, and hepatitis C in an acutely jaundiced patient with hepatitis of fulminant liver failure
Anti-HBc IgM
Anti-HAV IgM
Anti-Hep C
Chronic hepatitisHBsAgTo diagnose HBV infection: if positive for HBsAg to determine infectivity
HBeAgIf HBsAg patient worsens or is very ill, to diagnose concomitant infection with hepatitis delta virus
Anti-HBe
Anti-HDV (total + IgM)
Monitoring 
Infant follow-upHBsAgTo monitor the success of vaccination and passive immunization for perinatal transmission of HBV 12 15 mo after birth
Anti-HBc
Anti-HBs
Postvaccination screeningAnti-HBsTo ensure immunity has been achieved after vaccination (CDC recommends "titer" determination, but usually qualitative assay is adequate)
Sexual contactHBsAgTo monitor sexual partners of a patient with chronic HBV or hepatitis C

Anti-HBc

Anti-Hep C


aSee Abbreviations for definition of abbreviations.

Table 4 4 Interpretation of Viral Hepatitis Serologic Testing Patterns


Anti-HAV (IgM)HBsAgAnti-HBc (IgM)Anti-HBc (Total)Anti-C (ELISA)Interpretation
+ Acute hepatitis A
++ + Acute hepatitis A in hepatitis B carrier
+ + Chronic hepatitis Ba
 
++ Acute hepatitis B
+++ Acute hepatitis B
+ Past hepatitis B infection
+Hepatitis Cb
 
Early hepatitis C or other cause (other virus, toxin)

aPatients with chronic hepatitis B (either active hepatitis or carrier state) should have HBeAg and anti-HBe checked to determine activity of infection and relative infectivity. Anti-HBs is used to determine response to hepatitis B vaccination.

bAnti-C often takes 3 6 mo before being positive. PCR may allow earlier detection.

Figure 4 1.


Hepatitis A diagnostic profile. See individual tests in text. (Based on data from Abbott Laboratories, Diagnostic Division, North Chicago, Illinois. Used with permission.)


Figure 4 2.


Hepatitis B diagnostic profile. See individual tests in text. (Based on data from Abbott Laboratories, Diagnostic Division, North Chicago, Illinois. Used with permission.)

Hepatitis tests Collection: Tiger top tube

Hepatitis A

Anti-HAV Ab:

Total antibody to hepatitis A virus; confirms previous exposure to hepatitis A virus, elevated for life

Anti-HAV IgM:

IgM antibody to hepatitis A virus; indicative of recent infection with hepatitis A virus; declines typically 1 6 mo after symptoms

Hepatitis B

HBsAg:

Hepatitis B surface antigen. Earliest marker of HBV infection; indicates chronic or acute infection. Used by blood banks to screen donors; vaccination does not affect this test

Anti-HBc-Total:

IgG and IgM antibody to hepatitis B core antigen; confirms either previous exposure to hepatitis B virus (HBV) or ongoing infection. Used by blood banks to screen donors

Anti-HBc IgM:

IgM antibody to hepatitis B core antigen. Early and best indicator of acute infection with hepatitis B

HBeAg:

Hepatitis Be antigen; indicates infectivity. Order only when evaluating for chronic HBV infection

HBV-DNA:

Most sensitive and specific early evaluation of hepatitis B; may be detectable when all other markers are negative

Anti-HBe:

Antibody to hepatitis Be antigen; associated with resolution of active inflammation

Anti-HBs:

Antibody to hepatitis B surface antigen; indicates immunity and clinical recovery from infection or previous immunization with hepatitis B vaccine. Use to assess effectiveness of vaccine; request titer levels

Anti-HDV:

Total antibody to delta hepatitis; confirms previous exposure. Use with known acute or chronic HBV infection

Anti-HDV IgM:

IgM antibody to delta hepatitis; indicates recent infection. Use in known acute or chronic HBV infection

Hepatitis C

Anti-HCV:

Antibody against hepatitis C. Indicative of active viral replication and infectivity. Used by blood banks to screen donors. Many false-positives

HCV-RNA:

Nucleic acid probe detection of current HCV infection

High-Density Lipoprotein Cholesterol

See Cholesterol.

HLA (Human Leukocyte Antigens; HLA Typing)

Collection: Green top tube

Used to identify a group of antigens on the cell surface that are the primary determinants of histocompatibility; useful in assessing transplantation compatibility. Some HLA antigens are associated with specific diseases but are not diagnostic of these diseases.

HLA-B27:

Ankylosing spondylitis, psoriatic arthritis, Reiter syndrome, juvenile RA

HLA-DR4/HLA DR2:

Chronic Lyme disease arthritis

HLA-DRw2:

MS

HLA-B8:

Addison disease, juvenile-onset diabetes, Graves disease, gluten enteropathy

Homocysteine, Serum

Normal fasting 5 15 mol/L Fasting target < 10 mol/L

An independent risk factor for CAD and atherosclerosis. Moderate, intermediate, and severe hyperhomocysteinemia refer to concentrations 16 30, 31 100, and > 100 mol/L, respectively. May be useful for screening high-risk patients and recommendation of strategies for obtaining target of < 10 mol/L (ie, dietary, lifestyle changes, vitamin supplementation)

Increased:

Vitamin B12, B6, and folate deficiency, renal failure, medications (nicotinic acid, theophylline, methotrexate, levodopa, anticonvulsants) advanced age, hypothyroidism, impaired kidney function, SLE, certain medications, disorders of methionine metabolism and in nonfasting state

Human Chorionic Gonadotropin, Serum (HCG)

Normal, < 3.0 mIU/mL 10 d after conception > 3 mIU/mL 30 d, 100 5000 mIU/mL 10 wk, 50,000 140,000 mIU/mL > 16 wk, 10,000 50,000 mIU/mL Thereafter levels slowly decline Collection: Tiger top tube

Increased:

PRG, some testicular tumors (nonseminomatous germ cell tumors, but not seminoma), trophoblastic disease (hydatidiform mole, choriocarcinoma levels usually > 100,000 mIU/mL)

Human Immunodeficiency Virus (HIV) Testing

See Figure 4 3, CDC guidelines. Any HIV-positive person > 13 y with a CD4+ T-cell level < 200/mL or an HIV-positive patient with a CDC-defined indicator condition (eg, pulmonary candidiasis, disseminated histoplasmosis, HIV wasting, Kaposi sarcoma, TB, various lymphomas, PCP, and others) is considered to have AIDS. Confidentiality in HIV testing is regulated by law. Most states require consent for HIV testing. Release of HIV information by phone is likewise prohibited in most states. This information is normally released only in writing to the ordering attending physician on a confidential basis.

Figure 4 3.


Diagnostic algorithm for HIV infection. See individual tests in text. (Based on data from GlaxoSmithKline, Research Triangle Park, North Carolina. Used with permission.)

HIV Antibody

Normal = negative Collection: Tiger top tube

Recognize both HIV-1 and HIV-2 antibodies. Uses: diagnosis of AIDS and blood screening for transfusion. Antibodies develop 1 4 mo after infection.

HIV Antibody, ELISA

Normal = negative

Initial screen to detect HIV antibody; positive test is repeated or confirmed by Western blot.

Positive:

AIDS, asymptomatic HIV infection, if indeterminate, repeat in 1 mo or perform PCR for HIV-1 DNA or RNA

False-Positive:

Autoimmune or connective tissue diseases, hyperbilirubinemia, HLA antibodies, flu vaccine within 3 mo, hemophilia, rheumatoid factor, alcoholic hepatitis, dialysis patients

False-Negative:

Acute seroconversion (first 3 4 wk of HIV infection), advanced AIDS, autoimmune disease, renal failure and hemodialysis, cystic fibrosis, multiple PRGs or transfusions, liver disease, injectable drug use, vaccination

HIV PCR, DNA

Normal = negative

Performed on peripheral blood mononuclear cells, most sensitive assay for diagnosing infection; preferred test to diagnose HIV in children < 18 mo

HIV PCR, RNA

Normal = undetectable

Quantifies "viral load." Establishes diagnosis before antibody production or when HIV antibody is indeterminate. Obtained at baseline, an important piece of information for modifying HIV therapy (see below, HIV Plasma Viral Load). Not recommended for children < 18 mo

HIV Plasma Viral Load Test (PVL Test)

Interpretation: viral load < 500 HIV RNA copies/mL, low; viral load < 40,000 HIV RNA copies/mL, high. Use same assay for serial plasma viral load testing. Best predictor of progression to AIDS and death among HIV-infected persons. Used as a baseline and for initiation or modification of HIV therapy but not for diagnosis. Initiation of antiretroviral drug therapy is usually recommended when the PVL is 10,000 to 30,000 copies/mL or when CD4+ counts are < 350 500/mm3 (0.35 0.50 x 109/L). PVL levels usually show a 1- to 2-log reduction within 4 6 wk after therapy is started; goal is no detectable virus in 16 24 wk. The methods are

  • PCR most common; results reported as copies/mL of plasma.
  • bDNA (branched-chain DNA assay) reported as units/mL of plasma.
  • NASBA (nucleic acid sequence based amplification) infrequently used; reported units/mL of plasma.

Increased:

Acute HIV infection, clinical AIDS, disease progression, drug resistance

Decreased:

Response to therapy, remission

HIV Western Blot

Normal = negative

The reference procedure for confirming the presence or absence of HIV antibody.

Immunoglobulins, Quantitative

IgG: 65 1500 mg/dL IgM: 40 345 mg/dL IgA: 76 390 mg/dL IgE: 0 380 IU/mL IgD: 0 8 mg/dL Collection: Tiger top or red top

Used to evaluate immunodeficiency diseases; during replacement therapy, to evaluate humoral immunity

Increased:

Multiple myeloma (myeloma immunoglobulin increased, other immunoglobulins decreased); Waldenstr m macroglobulinemia (IgM increased, others decreased); lymphoma; carcinoma; bacterial infection; liver disease; sarcoidosis; amyloidosis; myeloproliferative disorders; IgE increased in allergic states

Decreased:

Hereditary immunodeficiency, leukemia, lymphoma, nephrotic syndrome, protein-losing enteropathy, malnutrition, transient hypogammaglobulinemia of infancy

Iron

Men: 55 160 mcg/dL Women: 40 155 mcg/dL Collection: Tiger top or red top tube

Increased:

Hemochromatosis, hemosiderosis caused by excessive iron intake, excess destruction or decreased production of erythrocytes, liver necrosis

Decreased:

Iron deficiency anemia, nephrosis (loss of iron-binding proteins), normochromic anemia of chronic diseases and infections

Iron-Binding Capacity, Total (TIBC)

250 400 mg/dL Collection: Tiger top or red top tube

Normal iron/TIBC ratio: 20 50%. Decreased ratio (< 10%) diagnostic of iron deficiency anemia. Increased ratio in hemochromatosis

Increased:

Acute and chronic blood loss, iron deficiency anemia, hepatitis, oral contraceptives

Decreased:

Anemia of chronic diseases, cirrhosis, nephrosis/uremia, hemochromatosis, iron therapy overload, hemolytic anemia, aplastic anemia, thalassemia, megaloblastic anemia

Lactate Dehydrogenase (LD, LDH)

Adults < 230 U/L Higher in childhood Collection: Tiger top or red top tube; avoid hemolysis, which can increase LDH

Increased:

AMI, cardiac surgery, prosthetic valve, hepatitis, pernicious anemia, malignant tumors, PE, hemolysis (anemias or factitious), renal infarction, muscle injury, megaloblastic anemia, liver disease

LDH Isoenzymes (LDH 1 to LDH 5)

Normal ratio LDH 1/LDH 2 < 0.6 0.7. Ratio > 1 (also called "flipped"), suspect recent MI (can also be seen in pernicious or hemolytic anemia). With AMI, LDH begins to rise 12 48 h after MI, peaks at 3 6 d, and returns to normal at 8 14 d. LDH 5 is > LDH 4 in liver disease. (Note: Troponin is considered marker of choice for AMI.)

Lactic Acid (Lactate)

4.5 19.8 mg/dL Collection: Gray top tube on ice

Suspect lactic acidosis with elevated anion gap in the absence of other causes (renal failure, ethanol or methanol ingestion).

Increased:

Lactic acidosis due to hypoxia, hemorrhage, shock, sepsis, cirrhosis, exercise, ethanol, DKA, regional ischemia (extremity, bowel) spurious factors (prolonged use of a tourniquet)

LAP Score (Leukocyte Alkaline Phosphatase Score/Stain)

50 150 Collection: Fingerstick blood sample directly on slide; smear and air dry

Differential diagnosis of CML versus leukemoid reaction; evaluation of polycythemia vera, myelofibrosis with myeloid metaplasia, and paroxysmal nocturnal hemoglobinuria

Increased:

Leukemoid reaction, acute inflammation, Hodgkin disease, PRG, liver disease, polycythemia vera

Decreased:

CML, nephrotic syndrome

LE (Lupus Erythematosus) Preparation

Normal = no cells seen

Positive:

SLE, scleroderma, RA, drug-induced lupus (procainamide, others)

Lead, Blood

Adult < 70 mcg/dL Child < 20 mg/dL Collection: Lavender, navy, or green top tube; lab-specific

Neurologic findings at 15 mg/dL in children and 30 mg/dL in adults; severe symptoms (lethargy, ataxia, coma) > 60 mg/dL

Increased:

Lead poisoning, occupational exposure

Legionella Antibody

Normal: < 1:32 titers Collection: Tiger top or red top tube

Obtain two serum samples: acute (within 2 wk of onset) and convalescent (at least 3 wk after onset of fever). A fourfold rise in titers or a single titer of 1:256 is diagnostic.

Increased:

Legionella infection; false-positives with Bacteroides fragilis, Francisella tularensis, Mycoplasma pneumoniae

Lipase

< 52 U/L (method dependent) Collection: Tiger top tube

Increased:

Acute or chronic pancreatitis, pseudocyst, pancreatic duct obstruction (stone, stricture, tumor, drug-induced spasm), fat embolus syndrome, renal failure, dialysis, usually normal in mumps, malignant gastric tumor, intestinal perforation, diabetes (usually in DKA only)

Lipid Profile/Lipoprotein Profile/Lipoprotein Analysis

See also Cholesterol and Triglycerides.

Usually includes cholesterol, HDL cholesterol, LDL cholesterol (calculated), triglycerides. Initial screening for cardiac risk includes total cholesterol, LDL, and HDL as outlined in Table 4 1. The main blood lipids, ie, cholesterol and triglycerides, are carried by lipoproteins. Lipoproteins are classified by density (least dense to most dense):

  • Chylomicrons least dense, rise to surface of unspun serum; normally found only after a fatty meal is eaten (a "lipemic specimen" refers to the presence of these chylomicrons)
  • VLDL mainly of triglycerides. With triglycerides < 400 mg/dL, the ratio of cholesterol to triglycerides is 1:5 in VLDL.
  • LDL carries most cholesterol in fasting state.
  • HDL densest and consists of mostly apoproteins and cholesterol

Low-Density Lipoprotein-Cholesterol (LDL, LDL-C)

See Cholesterol.

Luteinizing Hormone, Serum (LH)

Men: 1 13 IU/L Women (follicular or luteal): 6 30 IU/L midcycle peak increases two- to threefold over follicular or luteal, postmenopausal > 12 55 IU/L Collection: Tiger top or red top tube

Increased:

(Hypergonadotropic > 40 IU/L) postmenopause, surgical or radiation castration, ovarian or testicular failure, polycystic ovaries

Decreased:

(Hypogonadotropic < 40 IU/L prepubertal) hypothalamic or pituitary dysfunction, Kallmann syndrome, LHRH analogue therapy

Lyme Disease Serology

Normal varies with lab assay, ELISA < 1:8 Western blot nonreactive

Most useful for comparing acute and convalescent serum levels for relative titers. IgM antibody detectable 2 4 wk after onset of rash; IgG rises in 4 6 wk and peaks up to 6 mo after infection and may stay elevated for months to years.

Positive:

Infection with Borrelia burgdorferi, syphilis, and other rickettsial diseases. Confirm positive with Western blot with multiple bands of identity

Negative:

After antibiotic therapy or during first few weeks of disease

Magnesium

1.3 2.1 mg/dL Collection: Tiger top or red top tube

Increased:

Renal failure, hypothyroidism, magnesium-containing antacids, Addison disease, diabetic coma, severe dehydration, lithium intoxication

Decreased:

Malabsorption, steatorrhea, alcoholism and cirrhosis, hyperthyroidism, aldosteronism, diuretics, acute pancreatitis, hyperparathyroidism, hyperalimentation, NG suctioning, chronic dialysis, renal tubular acidosis, drugs (cisplatin, amphotericin B, aminoglycosides), hungry bone syndrome, hypophosphatemia, intracellular shifts with respiratory or metabolic acidosis

MHA-TP (Microhemagglutination, Treponema Pallidum)

Normal < 1:160 Collection: Tiger top tube

Confirmatory test for syphilis, similar to FTA-ABS. Once positive, remains so; do not use to judge treatment effect. False-positives: other treponemal infections (eg, pinta, yaws), mononucleosis, SLE

2-Microglobulin

0.07 0.18 mcg/dL Collection: Tiger top or red top tube

A portion of the class I MHC antigen; useful marker for following progression of HIV and B-cell malignancies (eg, multiple myeloma); levels < 4 mcg/d/L good prognosis in multiple myeloma

Increased:

HIV infection, especially during periods of exacerbation, lymphoid malignant diseases, renal diseases (diabetic nephropathy, pyelonephritis, ATN, nephrotoxicity from medications), transplant rejection, inflammatory conditions

Decreased:

Treatment of HIV with AZT (zidovudine)

Monospot

Normal = negative Collection: Tiger top or red top tube

Positive:

Mononucleosis, rarely in leukemia, serum sickness, Burkitt lymphoma, viral hepatitis, RA

Myoglobin

30 90 ng/mL Collection: Tiger top tube

Increased:

Skeletal muscle injury (crush, injection, surgical procedure), delirium tremens, rhabdomyolysis (burns, seizures, sepsis, hypokalemia, others), AMI (6 12 h after)

Natriuretic Peptide, B-Type (BNP)

< 100 pg/mL normal Collection: Lavender top tube on ice

BNP released by the ventricular myocardium secondary to volume and pressure overload. BNP increases sodium and water excretion. CHF severity correlates with BNP level (< 100 pg/mL rules out CHF, 100 400 pg/mL is borderline, > 400 pg/mL is highly suggestive of CHF). BNP used to differentiate CHF and other causes of dyspnea (eg, COPD).

Increased:

CHF/left ventricular dysfunction. Note: cross-reacts with IV nesiritide (Natrecor)

Natriuretic Peptide, NT-Pro B-Type, Plasma

Normal: < 200 pg/mL Collection: lavender top tube

With ventricular volume expansion and/or pressure overload, Pro BNP is cleaved to release "active" BNP (see Natriuretic Peptide, B-Type [BNP]), and the "inactive" N-terminal (NT) called NT-Pro BNP. Both BNP and NT-Pro BNP are markers of atrial and ventricular distension. Levels < 200 pg/mL exclude CHF, 200 400 pg/mL indicates compensated CHF, 400 2,000 pg/mL suggests moderate CHF, and > 2000 is consistent with moderate to severe CHF. NT-Pro-BNP advantages over BNP: greater stability, longer half-life, not cross-reactive with recombinant BNP (nesiritide, Natrecor). May provide more prognostic information than traditional risk factors

Increased:

CHF/left ventricular dysfunction

Newborn Screening Panel

Newborn screening varies by state law and is used to evaluate for a variety of inherited conditions: Phenylalanine (phenylketonuria); leucine (branched-chain ketonuria); galactose-1-phosphate uridyl transferase (galactosemia); methionine (homocystinuria); thyroxine, TSH (hypothyroidism); hemoglobin electrophoresis (sickle cell); biotinidase (biotinidase deficiency)

5'-Nucleotidase

2 15 U/L Collection: Tiger top or red top tube

Uses: work-up of increased alkaline phosphatase and biliary obstruction

Increased:

Obstructive or cholestatic liver disease, liver metastasis, biliary cirrhosis

Oligoclonal Banding, CSF

Normal = negative Collection: Tiger top or red top tube and simultaneous CSF sample collected in a plain tube by LP

Performed simultaneously on CSF and serum samples when MS is suspected. Agarose gel electrophoresis reveals multiple bands in the IgG region not seen in the serum with a positive test. Oligoclonal banding is present in as many as 90% of patients with MS. Occasionally seen in other CNS inflammatory conditions and CNS syphilis

Osmolality, Serum

278 298 mOsm/kg Collection: Tiger top tube

A rough estimation of osmolality is [2(Na) + BUN/2.8 + glucose/18]. Measured value is usually less than calculated value. If measured value is 15 mOsm/kg less than calculated, consider methanol, ethanol, or ethylene glycol ingestion or another unmeasured substance.

Increased:

Hyperglycemia; ethanol, methanol, mannitol, or ethylene glycol ingestion; increased sodium because of water loss (diabetes, hypercalcemia, diuresis)

Decreased:

Low serum sodium, diuretics, Addison disease, SIADH (seen in bronchogenic carcinoma, hypothyroidism), iatrogenic causes (poor fluid balance)

Oxygen

See Chapter 8, Table 8 1.

Parathyroid Hormone (PTH) Intact

10 60 pg/mL (method dependent) Collection: red top tube on ice; submit to lab immediately

The upper limit of the reference range may be lower in regions of the world with more daily hours of sunshine. If renal function is normal and serum calcium is elevated, an intact PTH concentration of > 50 pg/mL strongly suggests primary hyperparathyroidism.

Increased:

Primary hyperparathyroidism, secondary hyperparathyroidism (eg, hypocalcemia states such as chronic renal failure)

Decreased:

Hypoparathyroidism, hypercalcemia not due to hyperparathyroidism

Phosphorus

Adult 2.5 4.5 mg/dL Child 4.0 6.0 mg/dL Collection: Tiger top or red top tube

Increased:

Hypoparathyroidism (surgical, pseudohypoparathyroidism), excess vitamin D, secondary hyperparathyroidism, renal failure, bone disease (healing fractures), Addison disease, childhood, factitious increase (hemolysis of specimen)

Decreased:

Hyperparathyroidism, alcoholism, diabetes, hyperalimentation, acidosis, alkalosis, gout, salicylate poisoning, IV steroid, glucose or insulin administration, hypokalemia, hypomagnesemia, diuretics, vitamin D deficiency, phosphate-binding antacids

Potassium, Serum

3.5 5 mEq/L Collection: Tiger top or red top tube

Increased:

Factitious increase (hemolysis of specimen, thrombocytosis), renal failure, Addison disease, acidosis, spironolactone, triamterene, ACE inhibitors, dehydration, hemolysis, massive tissue damage, excess intake (oral or IV), potassium-containing medications

Decreased:

Diuretics, decreased intake, vomiting, NG suctioning, villous adenoma, diarrhea, Zollinger Ellison syndrome, chronic pyelonephritis, RTA, metabolic alkalosis (primary aldosteronism, Cushing syndrome)

Prealbumin

See Chapter 11.

Pregnancy Screening

Normal blood values based on gestational age, others based on chromosomal analysis. First-trimester screen offers advantages over second-trimester screen. Negative results reduce maternal anxiety. Positive results allow women to take advantage of first-trimester chorionic villus sampling (CVS) at 10 12 wk or second-trimester amniocentesis (15 weeks). American College of Obstetricians and Gynecologists recommends all women > 35 y at delivery be offered CVS or amniocentesis (diagnoses 99.9% of screened chromosomal abnormalities).

First Trimester Screening ("Combined Screening")

Maternal serum beta-HCG, PAPP-A (pregnancy associated plasma protein-A, with ultrasound-determined nuchal transparency)

Done at 11 13 wk. Screen of low-risk pregnant women (< 35 y) for Down syndrome and trisomy 18 (detects ~ 85% of cases of Down syndrome and ~ 97% of trisomy 18). Measures free beta-HCG and PAPP-A in combination with ultrasound assessment of fetal nuchal translucency (measure of fluid in the fetal neck).

Second Trimester Screening

("Quadruple screening") Maternal serum AFP, HCG, estriol, and inhibin A

Done at 15 21 wk of PRG to detect open neural tube defects, Down syndrome, and trisomy 18 (detects ~ 80% of open neural tube defects, ~ 85% of cases of Down syndrome, ~ 60% of cases of trisomy 18)

Chorionic Villus Sampling (CVS)

Performed at 10 12 wk of PRG; placental tissue removed percutaneously and studied for chromosomal analysis (~ 1% risk of complications such as miscarriage)

Amniocentesis

Performed at 13 14 wk of PRG (early amniocentesis) or at 15 wk and later (traditional amniocentesis). Chromosomal analysis is performed on the fetal skin cells in the amniotic fluid. Risk similar to CVS

Progesterone

Collection: Tiger top tube

Used to confirm ovulation and corpus luteum function

Sample Collection Normal Value (women) 
Follicular phase <1 ng/mL
Luteal phase 5 20 ng/mL
Pregnancy

   1st trimester 10 30 ng/mL
   2nd trimester 50 100 ng/mL
   3rd trimester 100 400 ng/mL
Postmenopause <1 ng/mL

Prolactin

Men: 1 20 ng/mL Women: 1 25 ng/mL Collection: Tiger top or red top tube

Used in work-up of infertility, impotence, hirsutism, amenorrhea, and pituitary neoplasm

Increased:

PRG, nursing after PRG, prolactinoma, hypothalamic tumors, sarcoidosis or granulomatous disease of the hypothalamus, hypothyroidism, renal failure, Addison disease, phenothiazines, haloperidol

Prostate-Specific Antigen (PSA)

< 4 ng/dL (some consider < 2.5 ng/dL normal)

Most useful as a measure of response to therapy of prostate cancer; approved for screening for prostate cancer

Increased:

Prostate cancer (levels > 10/dL increase likelihood of spread), acute prostatitis, BPH, prostatic infarction, prostate surgery (after biopsy, resection levels are elevated for 4 6 wk), vigorous prostatic massage (routine rectal exam does not elevate levels), rarely after ejaculation (some suggest refraining from sexual activity for 24 48 h before test)

Decreased:

Radical prostatectomy (should be "undetectable" or < 0.2 ng/dL), response to therapy for prostatic carcinoma (radiation or hormonal therapy), response to antibiotics in acute bacterial prostatitis

PSA Velocity/PSA Doubling Time

A rate of rise in PSA of > 0.75 ng/dL/y (velocity) is suggestive of prostate cancer on the basis of at least three separate assays 6 mo apart. Increased PSA doubling time < 3 mo before diagnosis or < 10 mo after treatment (radiation or surgery) suggests a poor prognosis.

PSA Free and Total

Prostate cancer tends to be associated with lower free PSA levels in proportion to total PSA; free/total PSA can improve the specificity of PSA in the range of total PSA from 2.0 10.0 ng/mL. Ratio free/total < 10% indicates > 50% chance of positive biopsy; > 25%, 8 10% risk of positive biopsy. Some recommend prostate biopsy only if the free PSA percentage is low; others use the ratio to guide further biopsy after an initial negative biopsy.

Protein Electrophoresis, Serum and Urine (Serum Protein Electrophoresis, SPEP) (Urine Protein Electrophoresis, UPEP)

Qualitative analysis of serum proteins is used in the work-up of hypoglobulinemia, macroglobulinemia, 1-antitrypsin deficiency, collagen disease, liver disease, and myeloma and occasionally in nutritional assessment. Serum electrophoresis yields five bands (Figure 4 4 and Table 4 5). If monoclonal gammopathy or a low globulin fraction is detected, quantitative immunoglobulin tests should be ordered. Urine protein electrophoresis can be used to evaluate proteinuria and to detect Bence Jones protein (light chain), which is associated with myeloma, Waldenstr m macroglobulinemia, and Fanconi syndrome.

Figure 4 4.


Examples of (A) serum and (B) urine electrophoresis patterns, See also Table 4 5. (Courtesy of Dr. Steven Haist.)

Table 4 5 Normal Serum Protein Components and Fractions as Determined by Electrophoresis, Along with Associated Conditionsa


Protein FractionPercentage of Total ProteinConstituentsIncreasedDecreased
Albumin52 68AlbuminDehydration (only known cause)Nephrosis, malnutrition, chronic liver disease
Alpha-1 (1) globulin
 
2.4 4.4Thyroxine-binding globulin, antitrypsin, lipoproteins, glycoprotein, transcortinInflammation, neoplasiaNephrosis, 1-antitrypsin deficiency (emphysema related)
 
Alpha-2 (2) globulin
 
6.1 10.1Haptoglobin, glycoprotein, macroglobulin, ceruloplasminInflammation, infection, neoplasia, cirrhosisSevere liver disease, acute hemolytic anemia
Beta () globulin8.5 14.5Transferrin, glycoprotein, lipoproteinCirrhosis, obstructive jaundiceNephrosis
Gamma () globulins (immunoglobulins)10 21IgA, IgG, IgM, IgD, IgEInfections, collagen-vascular diseases, leukemia, myelomaAgammaglobulinemia, hypogammaglobulinemia, nephrosis

a(See also Figure 4 4)

Protein, Serum

6.0 8.0 g/dL See also Serum Protein Electrophoresis. Collection: Tiger top or red top tube

Increased:

Multiple myeloma, Waldenstr m macroglobulinemia, benign monoclonal gammopathy, lymphoma, chronic inflammatory disease, sarcoidosis, viral illnesses

Decreased:

Malnutrition, inflammatory bowel disease, Hodgkin disease, leukemia, any cause of decreased albumin

Rapid Plasma Reagin (RPR) Test for Syphilis

Normal: nonreactive Collection: Tiger top or red top tube

Has replaced VDRL as the screening test for syphilis (T. pallidum). Confirm positive with a specific treponemal test (fluorescent treponemal antibody-absorbed (FTA-ABS) or microhemagglutination assay (TP-MHA). Not for testing CSF

Positive:

Syphilis; false-positives: other infections, pregnancy, drug addiction, collagen vascular disease

Renin, Plasma (Plasma Renin Activity [PRA])

Adults, normal-sodium diet, upright 1 6 ng/mL/h (position and method dependent) Collection: Lavender top tube, send to lab on ice

Used in work-up of HTN with hypokalemia. Values highly dependent on salt intake and position. Stop diuretics, estrogens for 2 4 wk before testing.

Increased:

Medications (ACE inhibitors, diuretics, oral contraceptives, estrogens), PRG, dehydration, renal artery stenosis, adrenal insufficiency, chronic hypokalemia, upright posture, salt-restricted diet, edematous conditions (CHF, nephrotic syndrome), secondary hyperaldosteronism

Decreased:

Primary aldosteronism (renin will not increase with relative volume depletion, upright posture)

Renin, Renal Vein

Normal L & R should be equal

A ratio of > 1.5 (affected/unaffected) suggestive of renovascular hypertension

Retinol-Binding Protein (RBP)

Adults 3 6 mg/dL Children 1.5 3.0 mg/dL Collection: Tiger top or red top tube

Decreased:

Malnutrition, vitamin A deficiency, intestinal malabsorption of fats, chronic liver disease

Increased:

Advanced chronic renal disease

Rheumatoid Factor (RF, RA Latex Test)

< 15 IU kit or > 1:40 Collection: Tiger top or red top tube

RF is an IgM autoantibody; may be negative early in the disease; a positive/elevated RF suggests more severe disease. Can be done on serum or synovial fluid. Initial work-up should include both RF and anti-CCP.

Increased:

RA (present in 80%); juvenile RA usually negative for RF, False-positives: other collagen vascular diseases (lupus erythematosus, scleroderma, Sj gren syndrome) hepatitis, cirrhosis of the liver, lymphomas, and other infections (endocarditis, tuberculosis, viral infections, chronic infections, hepatitis, chronic hepatic disease, syphilis); 1 2% of healthy persons and > 20% of healthy persons > 65 y

Decreased:

Anti-TNF-alpha therapy

Rocky Mountain Spotted Fever Antibodies (RMSF)

Normal: < 4x increase in paired acute and convalescent sera IgG < 1:64 IgM < 1:8 Collection: Tiger top tube or red top acute and convalescent

The diagnosis of RMSF is made with acute and convalescent titers that show a 4x increase or a single convalescent titer > 1:64 in the clinical setting of RMSF. Occasional false-positives in late PRG

Semen Analysis

Volume 2 5 mL Sperm count > 20 40 x 106/mL Motility > 60% Forward migration Morphology > 60% normal

Collect after 48 72 h abstinence, analyze in 1 2 h. May not be valid after a recent illness or high fever. Verify abnormal by serial tests.

Decreased:

After vasectomy (should be 0 sperm after 3 mo), varicocele, primary testicular failure (ie, Klinefelter syndrome), secondary testicular failure (chemotherapy, radiation, infections), varicocele, aftermath of recent illness, congenital obstruction of the vas, retrograde ejaculation, endocrine causes (eg, hyperprolactinemia, low testosterone)

Sodium, Serum

136 145 mmol/L Collection: Tiger top or red top tube

Increased:

Associated with low total body sodium (glycosuria, mannitol, or lactulose use, urea, excess sweating), normal total body sodium (diabetes insipidus [central and nephrogenic], respiratory losses, and sweating), and increased total body sodium (administration of hypertonic sodium bicarbonate, Cushing syndrome, hyperaldosteronism)

Decreased:

Associated with excess total body sodium and water (nephrotic syndrome, CHF, cirrhosis, renal failure), excess body water (SIADH [small-cell lung cancer; pulmonary disease including TB, lung cancer, pneumonia; CNS disease including trauma, tumors, and infections; perioperative stress; drugs including SSRIs and ACE inhibitors; and aftermath of colonoscopy], hypothyroidism, adrenal insufficiency, psychogenic polydipsia, beer potomania), decreased total body water and sodium (diuretic use, RTA, use of mannitol or urea, mineralocorticoid deficiency, cerebral salt wasting, vomiting, diarrhea, pancreatitis), and pseudohyponatremia (hyperlipidemia, hyperglycemia, multiple myeloma)

Stool for Occult Blood

See Fecal Occult Blood Test (FOBT), Hemoccult Test

Sweat Chloride

5 40 mEq/L Collection: 100 200 mg sweat on filter paper after electrical stimulation of sweating by pilocarpine iontophoresis on an extremity

Increased:

CF (not valid on children < 3 wk); Addison disease, meconium ileus, and renal failure can occasionally raise levels.

N-Telopeptide (NTX) (Urine and Serum)

Urine

Healthy women: Premenopausal 19 63 nM BCE/mM creatinine; Postmenopausal 26 124 nM BCE/mM creatinine Healthy men: 21 83 nM BCE/mM creatinine

Serum

Premenopausal women: 6.2 19.0 nM BCE Men > 25 y: 5.4 24.2 nM BCE

N-Telopeptides of type I collagen (NTx) are end products of bone resorption and allow monitoring of bone metabolism. Reported as nanomolar bone collagen equivalents per liter (nM BCE/L). In urine, values are corrected per millimolars of creatinine per liter (mM creatinine/L). Serum NTx provides a quantitative measurement of bone resorption. A baseline NTx level is obtained before antiresorptive therapy (ie, bisphosphonate) with periodic testing until decrease in NTx achieved

Increased:

Osteoporosis, Paget disease, primary hyperparathyroidism, bony metastasis

Decreased:

Response to bisphosphonate therapy (decrease of 30 40% from baseline after 3 mo of therapy is typical of bisphosphonate therapy)

Testosterone

Men: free 10 150 pg/mL, total 100 1100 ng/dL Women and girls: See following table

Age (y) Normal Value (women and girls) 
1 11 < 75 mg/dL
12 18 < 120 mg/dL
> 18 < 75 mg/dL
Postmenopausal < 50 mg/dL

Increased:

Adrenogenital syndrome, ovarian stromal hyperthecosis, polycystic ovaries, menopause, ovarian tumors

Decreased:

Hypogonadism, hypopituitarism, Klinefelter syndrome, male andropause

Thyroglobulin

< 33 ng/mL Collection: Tiger top or red top tube

Useful for following nonmedullary thyroid carcinoma

Increased:

Differentiated thyroid carcinoma (papillary, follicular), Graves disease, nontoxic goiter

Decreased:

Hypothyroidism, testosterone, steroids, phenytoin

Thyroid-Stimulating Hormone (TSH)

0.4 4.8 mIU/L Collection: Tiger top or red top tube

Best screen test for thyroid dysfunction; useful for monitoring thyroid replacement therapy and confirming TSH suppression in patients with thyroid cancer taking thyroxine therapy

Increased:

Primary hypothyroidism, values > 5 7 mIU/L suggest borderline or subclinical primary hypothyroidism

Decreased:

Primary hyperthyroidism, in secondary and tertiary hypothyroidism TSH levels can be decreased or normal (these cases make up less than 1% of all cases of hypothyroidism)

Thyroxine, Free (FT4)

Normal: 0.8 1.7 ng/dL Collection: Tiger top or red top tube

Confirms thyroid dysfunction after abnormal TSH. FT4 and TSH provide the best assessment of thyroid function in abnormal serum TBG levels or binding characteristics (eg, PRG, medication with estrogens, androgens, phenytoin, or salicylates). FT4 misleading with abnormal binding proteins or major illnesses that cause "euthyroid sick syndrome." Heparin, circulating free fatty acids, and antithyroxine autoantibodies can also cause aberrant results.

Increased:

Hyperthyroidism or exogenous thyroxine administration

Decreased:

Hypothyroidism

Torch Battery

Normal = negative Collection: Tiger top tube

Serial determinations best (acute and convalescent titers); based on serologic evidence of exposure to toxoplasmosis, rubella, CMV, and herpesviruses

Transferrin

210 360 mg/dL Collection: Tiger top or red top tube, avoid hemolysis

Used in work up of anemia; transferrin levels can also be assessed by total iron-binding capacity.

Increased:

Acute and chronic blood loss, iron deficiency, hemolysis, oral contraceptives, PRG, viral hepatitis

Decreased:

Anemia of chronic disease, cirrhosis, nephrosis, hemochromatosis, malignant diseases

Triglycerides

Recommended value: < 150 mg/dL; borderline high: 150 199 mg/dL; high 200 499 mg/dL; very high > 500 mg/dL Collection: Red top tube (Note: Tiger top tubes contain a silicone serum separator gel [SST] that interferes with triglycerides) Fasting required

Increased:

Nonfasting specimen hypothyroidism, liver diseases, poorly controlled DM, alcoholism, pancreatitis, AMI, nephrotic syndrome, familial disorders, medications (oral contraceptives, estrogens, beta-blockers, cholestyramine)

Decreased:

Malnutrition, malabsorption, hyperthyroidism, Tangier disease, medications (nicotinic acid, clofibrate, gemfibrozil), congenital abetalipoproteinemia

Triiodothyronine (T3)

80 200 ng/dL Collection: Red top tube

Used when hyperthyroidism suspected but T4 is normal (T3 thyrotoxicosis); not used to diagnose hypothyroidism

Increased:

Hyperthyroidism, T3 thyrotoxicosis, PRG, exogenous T4, any cause of increased TBG, eg, oral estrogen or PRG

Decreased:

Hypothyroidism and euthyroid sick state, any cause of decreased TBG

Troponin, Cardiac-Specific

Troponin I (TI) < 0.35 ng/mL Troponin T (TT) < 0.2 mcg/L (method dependent)

Used to diagnose AMI; increases rapidly 3 12 h after MI, peak at 24 h, and may stay elevated for several days (TI 5 7 d, TT up to 14 d). Serial testing recommended. More cardiac-specific than CK-MB

Positive:

Myocardial damage, including MI, myocarditis (false-positive: renal failure)

Uric Acid (Urate)

Men: 3.4 8 mg/dL Women: 2.4 6 mg/dL Collection: Tiger top or red top tube

Increase associated with increased catabolism, nucleoprotein synthesis, or decreased renal clearing of uric acid (ie, thiazide diuretics, renal failure)

Increased:

Gout, renal failure, destruction of massive amounts of nucleoproteins (leukemia, anemia, chemotherapy, toxemia of PRG), drugs (especially diuretics), lactic acidosis, hypothyroidism, PCKD, parathyroid diseases

Decreased:

Uricosuric drugs (salicylates, probenecid, allopurinol), Wilson disease, Fanconi syndrome

VDRL Test (Venereal Disease Research Laboratory)

VDRL is now approved only for testing CSF for syphilis. RPR (see Rapid Plasma Reagin [RPR] Test for Syphilis) is the standard screening test.

Vitamin B12 (Extrinsic Factor, Cyanocobalamin)

Normal 200 700 pg/mL Collection: Red top tube

Increased:

Excessive intake, myeloproliferative disorders

Decreased:

Inadequate intake (especially strict vegetarians), malabsorption, hyperthyroidism, PRG

Zinc

60 130 mcg/dL Collection: Check with lab; special collection to limit contamination

Increased:

Metal fume fever

Decreased:

Pernicious anemia, inadequate dietary intake (parenteral nutrition, alcoholism), malabsorption, increased needs (PRG, severe burns, wound healing), acrodermatitis enteropathica, dwarfism, hepatic disease


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Clinician's Pocket Reference
Clinicians Pocket Reference, 11th Edition
ISBN: 0071454284
EAN: 2147483647
Year: 2004
Pages: 30

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