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Subject: Lab Test Interpretation (monthly posting, 47K, version 2.1)
This article was archived around: 4 Mar 1998 19:48:37 GMT
Last-modified: September 10, 1997
Posting-Frequency: monthly (first Wednesday)
Maintainer: Ed Uthman <firstname.lastname@example.org>
INTERPRETATION OF LAB TEST PROFILES
Ed Uthman, MD <email@example.com>
Diplomate, American Board of Pathology
The various multiparameter blood chemistry and hematology profiles
offered by most labs represent an economical way by which a large
amount of information concerning a patient's physiologic status can be
made available to the physician. The purpose of this monograph is to
serve as a reference for the interpretation of abnormalities of each of
REFERENCE RANGES ("normal ranges")
Because reference ranges (except for some lipid studies) are
typically defined as the range of values of the median 95% of
the healthy population, it is unlikely that a given specimen,
even from a healthy patient, will show "normal" values for all
the tests in a lengthy profile. Therefore, caution should be
exercised to prevent overreaction to miscellaneous, mild
abnormalities without clinical correlate.
UNITS OF MEASUREMENT: America against the world
American labs use a different version of the metric system than
does most of the rest of the world, which uses the Systeme
Internationale (SI). In some cases translation between the two
systems is easy, but the difference between the two is most
pronounced in measurement of chemical concentration. The
American system generally uses mass per unit volume, while SI
uses moles per unit volume. Since mass per mole varies with the
molecular weight of the analyte, conversion between American and
SI units requires many different conversion factors. Where
appropriate, in this paper SI units are given after American
Increase in serum sodium is seen in conditions with water loss
in excess of salt loss, as in profuse sweating, severe diarrhea
or vomiting, polyuria (as in diabetes mellitus or insipidus),
hypergluco- or mineralocorticoidism, and inadequate water
intake. Drugs causing elevated sodium include steroids with
mineralocorticoid activity, carbenoxolone, diazoxide,
guanethidine, licorice, methyldopa, oxyphenbutazone, sodium
bicarbonate, methoxyflurane, and reserpine.
Decrease in sodium is seen in states characterized by intake of
free water or hypotonic solutions, as may occur in fluid
replacement following sweating, diarrhea, vomiting, and diuretic
abuse. Dilutional hyponatremia may occur in cardiac failure,
liver failure, nephrotic syndrome, malnutrition, and SIADH.
There are many other causes of hyponatremia, mostly related to
corticosteroid metabolic defects or renal tubular abnormalities.
Drugs other than diuretics may cause hyponatremia, including
ammonium chloride, chlorpropamide, heparin, aminoglutethimide,
vasopressin, cyclophosphamide, and vincristine.
Increase in serum potassium is seen in states characterized by
excess destruction of cells, with redistribution of K+ from the
intra- to the extracellular compartment, as in massive
hemolysis, crush injuries, hyperkinetic activity, and malignant
hyperpyrexia. Decreased renal K+ excretion is seen in acute
renal failure, some cases of chronic renal failure, Addison's
disease, and other sodium-depleted states. Hyperkalemia due to
pure excess of K+ intake is usually iatrogenic.
Drugs causing hyperkalemia include amiloride, aminocaproic acid,
antineoplastic agents, epinephrine, heparin, histamine,
indomethacin, isoniazid, lithium, mannitol, methicillin,
potassium salts of penicillin, phenformin, propranolol, salt
substitutes, spironolactone, succinylcholine, tetracycline,
triamterene, and tromethamine. Spurious hyperkalemia can be seen
when a patient exercises his/her arm with the tourniquet in
place prior to venipuncture. Hemolysis and marked thrombocytosis
may cause false elevations of serum K+ as well. Failure to
promptly separate serum from cells in a clot tube is a notorious
source of falsely elevated potassium.
Decrease in serum potassium is seen usually in states
characterized by excess K+ loss, such as in vomiting, diarrhea,
villous adenoma of the colorectum, certain renal tubular
defects, hypercorticoidism, etc. Redistribution hypokalemia is
seen in glucose/insulin therapy, alkalosis (where serum K+ is
lost into cells and into urine), and familial periodic
paralysis. Drugs causing hypokalemia include amphotericin,
carbenicillin, carbenoxolone, corticosteroids, diuretics,
licorice, salicylates, and ticarcillin.
Increase in serum chloride is seen in dehydration, renal
tubular acidosis, acute renal failure, diabetes insipidus,
prolonged diarrhea, salicylate toxicity, respiratory alkalosis,
hypothalamic lesions, and adrenocortical hyperfunction. Drugs
causing increased chloride include acetazolamide, androgens,
corticosteroids, cholestyramine, diazoxide, estrogens,
guanethidine, methyldopa, oxyphenbutazone, phenylbutazone,
thiazides, and triamterene. Bromides in serum will not be
distinguished from chloride in routine testing, so intoxication
may show spuriously increased chloride [see also "Anion gap,"
Decrease in serum chloride is seen in excessive sweating,
prolonged vomiting, salt-losing nephropathy, adrenocortical
defficiency, various acid base disturbances, conditions
characterized by expansion of extracellular fluid volume, acute
intermittent porphyria, SIADH, etc. Drugs causing decreased
chloride include bicarbonate, carbenoxolone, corticosteroids,
diuretics, laxatives, and theophylline.
Increase in serum CO2 content for the most part reflects
increase in serum bicarbonate (HCO3-) concentration rather than
dissolved CO2 gas, or PCO2 (which accounts for only a small
fraction of the total). Increased serum bicarbonate is seen in
compensated respiratory acidosis and in metabolic alkalosis.
Diuretics (thiazides, ethacrynic acid, furosemide, mercurials),
corticosteroids (in long term use), and laxatives (when abused)
may cause increased bicarbonate.
Decrease in blood CO2 is seen in metabolic acidosis and
compensated respiratory alkalosis. Substances causing metabolic
acidosis include ammonium chloride, acetazolamide, ethylene
glycol, methanol, paraldehyde, and phenformin. Salicylate
poisoning is characterized by early respiratory alkalosis
followed by metabolic acidosis with attendant decreased
Critical studies on bicarbonate are best done on anaerobically
collected heparinized whole blood (as for blood gas
determination) because of interaction of blood and atmosphere in
routinely collected serum specimens. Routine electrolyte panels
are usually not collected in this manner.
The tests "total CO2" and "CO2 content" measure essentially the
same thing. The "PCO2" component of blood gas analysis is a test
of the ventilatory component of pulmonary function only.
Increased serum anion gap reflects the presence of unmeasured
anions, as in uremia (phosphate, sulfate), diabetic ketoacidosis
(acetoacetate, beta-hydroxybutyrate), shock, exercise-induced
physiologic anaerobic glycolysis, fructose and phenformin
administration (lactate), and poisoning by methanol (formate),
ethylene glycol (oxalate), paraldehyde, and salicylates. Therapy
with diuretics, penicillin, and carbenicillin may also elevate
the anion gap.
Decreased serum anion gap is seen in dilutional states and
hyperviscosity syndromes associated with paraproteinemias.
Because bromide is not distinguished from chloride in some
methodologies, bromide intoxication may appear to produce a
decreased anion gap.
Hyperglycemia can be diagnosed only in relation to time
elapsed after meals and after ruling out spurious influences
(especially drugs, including caffeine, corticosteroids,
estrogens, indomethacin, oral contraceptives, lithium,
phenytoin, furosemide, thiazides, thyroxine, and many more).
Generally, fasting blood glucose >140 mg/dL (7.8mmol/L) and/or
2h postprandial glucose >200 mg/dL (11.1 mmol/L) demonstrated on
several occasions is suggestive of diabetes mellitus; oral
glucose tolerance test is usually not required for diagnosis.
In adults, hypoglycemia can be observed in certain neoplasms
(islet cell tumor, adrenal and gastric carcinoma, fibrosarcoma,
hepatoma), severe liver disease, poisonings (arsenic, CCl4,
chloroform, cinchophen, phosphorous, alcohol, salicylates,
phenformin, and antihistamines), adrenocortical insufficiency,
hypothroidism, and functional disorders (postgastrectomy,
gastroenterostomy, autonomic nervous system disorders). Failure
to promptly separate serum from cells in a blood collection tube
causes falsely depressed glucose levels. If delay in
transporting a blood glucose to the lab is anticipated, the
specimen should be collected in a fluoride-containing tube
(gray-top in the US, yellow in the UK).
UREA NITROGEN (BUN)
Serum urea nitrogen (BUN) is increased in acute and chronic
intrinsic renal disease, in states characterized by decreased
effective circulating blood volume with decreased renal
perfusion, in postrenal obstruction of urine flow, and in high
protein intake states.
Decreased serum urea nitrogen (BUN) is seen in high
carbohydrate/low protein diets, states characterized by
increased anabolic demand (late pregnancy, infancy, acromegaly),
malabsorption states, and severe liver damage.
In Europe, the test is called simply "urea."
Increase in serum creatinine is seen any renal functional
impairment. Because of its insensitivity in detecting early
renal failure, the creatinine clearance is significantly reduced
before any rise in serum creatinine occurs. The renal impairment
may be due to intrinsic renal lesions, decreased perfusion of
the kidney, or obstruction of the lower urinary tract.
Nephrotoxic drugs and other chemicals include:
antimony arsenic bismuth cadmium
copper gold iron lead
lithium mercury silver thallium
uranium aminopyrine ibuprofen indomethacin
naproxen fenoprofen phenylbutazone phenacetin
salicylates aminoglycosides amphotericin cephalothin
colistin cotrimoxazole erythromycin ampicillin
methicillin oxacillin polymixin B rifampin
sulfonamides tetracyclines vancomycin benzene
zoxazolamine tetrachloroethylene ethylene glycol
acetazolamide aminocaproic acid aminosalicylate boric acid
cyclophosphamide cisplatin dextran (LMW) furosemide
mannitol methoxyflurane mithramycin penicillamine
pentamide phenindione quinine thiazides
Deranged metabolic processes may cause increases in serum
creatinine, as in acromegaly and hyperthyroidism, but dietary
protein intake does not influence the serum level (as opposed to
the situation with BUN). Some substances interfere with the
colorimetric system used to measure creatinine, including
acetoacetate, ascorbic acid, levodopa, methyldopa, glucose and
fructose. Decrease in serum creatinine is seen in pregnancy and
in conditions characterized by muscle wasting.
BUN:creatinine ratio is usually >20:1 in prerenal and postrenal
azotemia, and <12:1 in acute tubular necrosis. Other intrinsic
renal disease characteristically produces a ratio between these
The BUN:creatinine ratio is not widely reported in the UK.
Increase in serum uric acid is seen idiopathically and in renal
failure, disseminated neoplasms, toxemia of pregnancy,
psoriasis, liver disease, sarcoidosis, ethanol consumption, etc.
Many drugs elevate uric acid, including most diuretics,
catecholamines, ethambutol, pyrazinamide, salicylates, and large
doses of nicotinic acid.
Decreased serum uric acid level may not be of clinical
significance. It has been reported in Wilson's disease,
Fanconi's syndrome, xanthinuria, and (paradoxically) in some
neoplasms, including Hodgkin's disease, myeloma, and
Hyperphosphatemia may occur in myeloma, Paget's disease of
bone, osseous metastases, Addison's disease, leukemia,
sarcoidosis, milk-alkali syndrome, vitamin D excess, healing
fractures, renal failure, hypoparathyroidism, diabetic
ketoacidosis, acromegaly, and malignant hyperpyrexia. Drugs
causing serum phosphorous elevation include androgens,
furosemide, growth hormone, hydrochlorthiazide, oral
contraceptives, parathormone, and phosphates.
Hypophosphatemia can be seen in a variety of biochemical
derangements, incl. acute alcohol intoxication, sepsis,
hypokalemia, malabsorption syndromes, hyperinsulinism,
hyperparathyroidism, and as result of drugs, e.g.,
acetazolamide, aluminum-containing antacids, anesthetic agents,
anticonvulsants, and estrogens (incl. oral contraceptives).
Citrates, mannitol, oxalate, tartrate, and phenothiazines may
produce spuriously low phosphorous by interference with the
Hypercalcemia is seen in malignant neoplasms (with or without
bone involvement), primary and tertiary hyperparathyroidism,
sarcoidosis, vitamin D intoxication, milk-alkali syndrome,
Paget's disease of bone (with immobilization), thyrotoxicosis,
acromegaly, and diuretic phase of renal acute tubular necrosis.
For a given total calcium level, acidosis increases the
physiologically active ionized form of calcium. Prolonged
tourniquet pressure during venipuncture may spuriously increase
total calcium. Drugs producing hypercalcemia include alkaline
antacids, DES, diuretics (chronic administration), estrogens
(incl. oral contraceptives), and progesterone.
Hypocalcemia must be interpreted in relation to serum albumin
concentration (Some laboratories report a "corrected calcium" or
"adjusted calcium" which relate the calcium assay to a normal
albumin. The normal albumin, and hence the calculation, varies
from laboratory to laboratory). True decrease in the
physiologically active ionized form of Ca++ occurs in many
situations, including hypoparathyroidism, vitamin D deficiency,
chronic renal failure, Mg++ deficiency, prolonged anticonvulsant
therapy, acute pancreatitis, massive transfusion, alcoholism,
etc. Drugs producing hypocalcemiainclude most diuretics,
estrogens, fluorides, glucose, insulin, excessive laxatives,
magnesium salts, methicillin, and phosphates.
Serum iron may be increased in hemolytic, megaloblastic, and
aplastic anemias, and in hemochromatosis, acute leukemia, lead
poisoning, pyridoxine deficiency, thalassemia, excessive iron
therapy, and after repeated transfusions. Drugs causing
increased serum iron include chloramphenicol, cisplatin,
estrogens (including oral contraceptives), ethanol, iron
dextran, and methotrexate.
Iron can be decreased in iron-deficiency anemia, acute and
chronic infections, carcinoma, nephrotic syndrome,
hypothyroidism, in protein- calorie malnutrition, and after
ALKALINE PHOSPHATASE (ALP)
Increased serum alkaline phosphatase is seen in states of
increased osteoblastic activity (hyperparathyroidism,
osteomalacia, primary and metastatic neoplasms), hepatobiliary
diseases characterized by some degree of intra- or extrahepatic
cholestasis, and in sepsis, chronic inflammatory bowel disease,
and thyrotoxicosis. Isoenzyme determination may help determine
the organ/tissue responsible for an alkaline phosphatase
Decreased serum alkaline phosphatase may not be clinically
significant. However, decreased serum levels have been observed
in hypothyroidism, scurvy, kwashiokor, achrondroplastic
dwarfism, deposition of radioactive materials in bone, and in
the rare genetic condition hypophosphatasia.
There are probably more variations in the way in which alkaline
phosphatase is assayed than any other enzyme. Therefore, the
reporting units vary from place to place. The reference range
for the assaying laboratory must be carefully studied when
interpreting any individual result.
LACTATE DEHYDROGENASE (LD or "LDH")
Increase of LD activity in serum may occur in any injury that
causes loss of cell cytoplasm. More specific information can be
obtained by LD isoenzyme studies. Also, elevation of serum LD is
observed due to in vivo effects of anesthetic agents,
clofibrate, dicumarol, ethanol, fluorides, imipramine,
methotrexate, mithramycin, narcotic analgesics, nitrofurantoin,
propoxyphene, quinidine, and sulfonamides.
Decrease of serum LD is probably not clinically significant.
There are two main analytical methods for measuring LD:
pyruvate->lactate and lactate->pyruvate. Assay conditions
(particularly temperature) vary among labs. The reference range
for the assaying laboratory must be carefully studied when
interpreting any individual result.
Many European labs assay alpha-hydroxybutyrate dehydrogenase
(HBD or HBDH), which roughly equates to LD isoenzymes 1 and 2
(the fractions found in heart, red blood cells, and kidney).
Increase of serum alanine aminotransferase (ALT, formerly
called "SGPT") is seen in any condition involving necrosis of
hepatocytes, myocardial cells, erythrocytes, or skeletal muscle
cells. [See "Bilirubin, total," below]
Increase of aspartate aminotransferase (AST, formerly called
"SGOT") is seen in any condition involving necrosis of
hepatocytes, myocardial cells, or skeletal muscle cells. [See
"Bilirubin, total," below] Decreased serum AST is of no known
Gamma-glutamyltransferase is markedly increased in lesions
which cause intrahepatic or extrahepatic obstruction of bile
ducts, including parenchymatous liver diseases with a major
cholestatic component (e.g., cholestatic hepatitis). Lesser
elevations of gamma-GT are seen in other liver diseases, and in
infectious mononucleosis, hyperthyroidism, myotonic dystrophy,
and after renal allograft. Drugs causing hepatocellular damage
and cholestasis may also cause gamma-GT elevation (see under
"Total bilirubin," below).
Gamma-GT is a very sensitive test for liver damage, and
unexpected, unexplained mild elevations are common. Alcohol
consumption is a common culprit.
Decreased gamma-GT is not clinically significant.
Serum total bilirubin is increased in hepatocellular damage
(infectious hepatitis, alcoholic and other toxic hepatopathy,
neoplasms), intra- and extrahepatic biliary tract obstruction,
intravascular and extravascular hemolysis, physiologic neonatal
jaundice, Crigler-Najjar syndrome, Gilbert's disease,
Dubin-Johnson syndrome, and fructose intolerance.
Drugs known to cause cholestasis include the following:
aminosalicylic acid androgens azathioprine benzodiazepines
carbamazepine carbarsone chlorpropamide propoxyphene
estrogens penicillin gold Na thiomalate imipramine
meprobamate methimazole nicotinic acid progestins
penicillin phenothiazines oral contraceptives
sulfonamides sulfones erythromycin estolate
Drugs known to cause hepatocellular damage include the
acetaminophen allopurinol aminosalicylic acid amitriptyline
androgens asparaginase aspirin azathioprine
carbamazepine chlorambucil chloramphenicol chlorpropamide
dantrolene disulfiram estrogens ethanol
ethionamide halothane ibuprofen indomethacin
iron salts isoniazid MAO inhibitors mercaptopurine
methotrexate methoxyflurane methyldopa mithramycin
nicotinic acid nitrofurantoin oral contraceptives papaverine
paramethadione penicillin phenobarbital phenazopyridine
phenylbutazone phenytoin probenecid procainamide
propylthiouracil pyrazinamide quinidine sulfonamides
tetracyclines trimethadione valproic acid
Disproportionate elevation of direct (conjugated) bilirubin is
seen in cholestasis and late in the course of chronic liver
disease. Indirect (unconjugated) bilirubin tends to predominate
in hemolysis and Gilbert's disease.
Decreased serum total bilirubin is probably not of clinical
significance but has been observed in iron deficiency anemia.
Increase in serum total protein reflects increases in albumin,
globulin, or both. Generally significantly increased total
protein is seen in volume contraction, venous stasis, or in
Decrease in serum total protein reflects decreases in albumin,
globulin or both [see "Albumin" and "Globulin, A/G ratio,"
Increased absolute serum albumin content is not seen as a
natural condition. Relative increase may occur in
hemoconcentration. Absolute increase may occur artificially by
infusion of hyperoncotic albumin suspensions.
Decreased serum albumin is seen in states of decreased
synthesis (malnutrition, malabsorption, liver disease, and other
chronic diseases), increased loss (nephrotic syndrome, many GI
conditions, thermal burns, etc.), and increased catabolism
(thyrotoxicosis, cancer chemotherapy, Cushing's disease,
GLOBULIN, A/G RATIO
Globulin is increased disproportionately to albumin
(decreasing the albumin/globulin ratio) in states characterized
by chronic inflammation and in B-lymphocyte neoplasms, like
myeloma and Waldenström's macroglobulinemia. More relevant
information concerning increased globulin may be obtained by
serum protein electrophoresis.
Decreased globulin may be seen in congenital or acquired
hypogammaglobulinemic states. Serum and urine protein
electrophoresis may help to better define the clinical problem.
This test measures the amount of thyroxine-binding globulin
(TBG) in the patient's serum. When TBG is increased, T3 uptake
is decreased, and vice versa. T3 Uptake does not measure the
level of T3 or T4 in serum.
Increased T3 uptake (decreased TBG) in euthyroid patients is
seen in chronic liver disease, protein-losing states, and with
use of the following drugs: androgens, barbiturates,
bishydroxycourmarin, chlorpropamide, corticosteroids, danazol,
d-thyroxine, penicillin, phenylbutazone, valproic acid, and
androgens. It is also seen in hyperthyroidism.
Decreased T3 uptake (increased TBG) may occur due to the
effects of exogenous estrogens (including oral contraceptives),
pregnancy, acute hepatitis, and in genetically-determined
elevations of TBG. Drugs producing increased TBG include
clofibrate, lithium, methimazole, phenothiazines, and
propylthiouracil. Decreased T3 uptake may occur in
This is a measurement of the total thyroxine in the serum,
including both the physiologically active (free) form, and the
inactive form bound to thyroxine-binding globulin (TBG). It is
increased in hyperthyroidism and in euthyroid states
characterized by increased TBG (See "T3 uptake," above, and
"FTI," below). Occasionally, hyperthyroidism will not be
manifested by elevation of T4 (free or total), but only by
elevation of T3 (triiodothyronine). Therefore, if thyrotoxicosis
is clinically suspect, and T4 and FTI are normal, the test
"T3-RIA" is recommended (this is not the same test as "T3
uptake," which has nothing to do with the amount of T3 in the
T4 is decreased in hypothyroidism and in euthyroid states
characterized by decreased TBG. A separate test for "free T4" is
available, but it is not usually necessary for the diagnosis of
functional thyroid disorders.
This is a convenient parameter with mathematically accounts for
the reciprocal effects of T4 and T3 uptake to give a single
figure which correlates with free T4. Therefore, increased FTI
is seen in hyperthyroidism, and with decreased FTI is seen in
hypothyroidism. Early cases of hyperthyroidism may be expressed
only by decreased thyroid stimulation hormone (TSH) with normal
FTI. Early cases of hypothyroidism may be expressed only by
increased TSH with normal FTI.
ASSESSMENT OF ATHEROSCLEROSIS RISK: Triglycerides, Cholesterol,
HDL Cholesterol, LDL Cholesterol, Chol/HDL ratio
All of these studies find greatest utility in assessing the risk of
atherosclerosis in the patient. Increased risks based on lipid studies
are independent of other risk factors, such as cigarette smoking.
Total cholesterol has been found to correlate with total and
cardiovascular mortality in the 30-50 year age group. Cardiovascular
mortality increases 9% for each 10 mg/dL increase in total cholesterol
over the baseline value of 180 mg/dL. Approximately 80% of the adult
male population has values greater than this, so the use of the median
95% of the population to establish a normal range (as is traditional in
lab medicine in general) has no utility for this test. Excess mortality
has been shown not to correlate with cholesterol levels in the >50
years age group, probably because of the depressive effects on
cholesterol levels expressed by various chronic diseases to which older
individuals are prone.
HDL-cholesterol is "good" cholesterol, in that risk of cardiovascular
disease decreases with increase of HDL. One way to assess risk is to
use the total cholesterol/HDL-cholesterol ratio, with lower values
indicating lower risk. The following chart has been developed from
ideas advanced by Castelli and Levitas, Current Prescribing, June,
1977. It should be taken with a large grain of salt substitute:
Total cholesterol (mg/dL)
150 185 200 210 220 225 244 260 300
25 | #### 1.34 1.50 1.60 1.80 2.00 3.00 4.00 6.00
30 | #### 1.22 1.37 1.46 1.64 1.82 2.73 3.64 5.46
35 | #### 1.00 1.12 1.19 1.34 1.49 2.24 2.98 4.47
HDL-chol 40 | #### 0.82 0.92 0.98 1.10 1.22 1.83 2.44 3.66
(mg/dL) 45 | #### 0.67 0.75 0.80 0.90 1.00 1.50 2.00 3.00
50 | #### 0.55 0.62 0.66 0.74 0.82 1.23 1.64 2.46
55 | #### 0.45 0.50 0.54 0.60 0.67 1.01 1.34 2.01
60 | #### 0.37 0.41 0.44 0.50 0.55 0.83 1.10 1.65
65 | #### 0.30 0.34 0.36 0.41 0.45 0.68 0.90 1.35
over 70 | #### #### #### #### #### #### #### #### ####
The numbers with two-decimal format represent the relative risk of
atherosclerosis vis-a-vis the general population. Cells marked "####"
indicate very low risk or undefined risk situations. Some authors have
warned against putting too much emphasis on the total-chol/HDL-chol
ratio at the expense of the total cholesterol level.
Readers outside the US may find the following version of the table more
useful. This uses SI units for total and HDL cholesterol:
Total cholesterol (mmol/L)
3.9 4.8 5.2 5.4 5.7 5.8 6.3 6.7 7.8
0.65 | #### 1.34 1.50 1.60 1.80 2.00 3.00 4.00 6.00
0.78 | #### 1.22 1.37 1.46 1.64 1.82 2.73 3.64 5.46
0.91 | #### 1.00 1.12 1.19 1.34 1.49 2.24 2.98 4.47
HDL-chol 1.04 | #### 0.82 0.92 0.98 1.10 1.22 1.83 2.44 3.66
(mmol/L) 1.16 | #### 0.67 0.75 0.80 0.90 1.00 1.50 2.00 3.00
1.30 | #### 0.55 0.62 0.66 0.74 0.82 1.23 1.64 2.46
1.42 | #### 0.45 0.50 0.54 0.60 0.67 1.01 1.34 2.01
1.55 | #### 0.37 0.41 0.44 0.50 0.55 0.83 1.10 1.65
1.68 | #### 0.30 0.34 0.36 0.41 0.45 0.68 0.90 1.35
over 1.81 | #### #### #### #### #### #### #### #### ####
Triglyceride level is risk factor independent of the cholesterol
levels. Triglycerides are important as risk factors only if they are
not part of the chylomicron fraction. To make this determination in a
hypertriglyceridemic patient, it is necessary to either perform
lipoprotein electrophoresis or visually examine an overnight-
refrigerated serum sample for the presence of a chylomicron layer. The
use of lipoprotein electrophoresis for routine assessment of
atherosclerosis risk is probably overkill in terms of expense to the
LDL-cholesterol (the amount of cholesterol associated with low-density,
or beta, lipoprotein) is not an independently measured parameter but is
mathematically derived from the parameters detailed above. Some risk-
reduction programs use LDL-cholesterol as the primary target parameter
for monitoring the success of the program.
Markedly increased triglycerides (>500 mg/dL) usually indicate
a nonfasting patient (i.e., one having consumed any calories
within 12-14 hour period prior to specimen collection). If
patient is fasting, hypertriglyceridemia is seen in
hyperlipoproteinemia types I, IIb, III, IV, and V. Exact
classification theoretically requires lipoprotein
electrophoresis, but this is not usually necessary to assess a
patient's risk to atherosclerosis [See "Assessment of
Atherosclerosis Risk," above]. Cholestyramine, corticosteroids,
estrogens, ethanol, miconazole (intravenous), oral
contraceptives, spironolactone, stress, and high carbohydrate
intake are known to increase triglycerides. Decreased serum
triglycerides are seen in abetalipoproteinemia, chronic
obstructive pulmonary disease, hyperthyroidism, malnutrition,
and malabsorption states.
RBC (Red Blood Cell) COUNT
The RBC count is most useful as raw data for calculation of the
erythrocyte indices MCV and MCH [see below]. Decreased RBC is
usually seen in anemia of any cause with the possible exception
of thalassemia minor, where a mild or borderline anemia is seen
with a high or borderline-high RBC. Increased RBC is seen in
erythrocytotic states, whether absolute (polycythemia vera,
erythrocytosis of chronic hypoxia) or relative (dehydration,
stress polycthemia), and in thalassemia minor [see "Hemoglobin,"
below, for discussion of anemias and erythrocytoses].
HEMOGLOBIN, HEMATOCRIT, MCV (mean corpuscular volume), MCH
(mean corpuscular hemoglobin), MCHC (mean corpuscular
Strictly speaking, anemia is defined as a decrease in total body red
cell mass. For practical purposes, however, anemia is typically defined
as hemoglobin <12.0 g/dL and direct determination of total body RBC
mass is almost never used to establish this diagnosis. Anemias are then
classed by MCV and MCHC (MCH is usually not helpful) into one of the
A. Microcytic/hypochromic anemia (decreased MCV, decreased
Iron deficiency (common)
Thalassemia (common, except in people of Germanic,
Slavonic, Baltic, Native American, Han Chinese,
Anemia of chronic disease (uncommonly microcytic)
Sideroblastic anemia (uncommon; acquired forms more often
Lead poisoning (uncommon)
Hemoglobin E trait or disease (common in Thai, Khmer,
Burmese,Malay, Vietnamese, and Bengali groups)
B. Macrocytic/normochromic anemia (increased MCV, normal MCHC)
Folate deficiency (common)
B12 deficiency (common)
Myelodysplastic syndromes (not uncommon, especially in
C. Normochromic/normocytic anemia (normal MCV, normal MCHC)
The first step in laboratory workup of this broad class of
anemias is a reticulocyte count. Elevated reticulocytes implies
a normo-regenerative anemia, while a low or "normal" count
implies a hyporegenerative anemia:
1. Normoregenerative normocytic anemias (appropriate
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Hemoglobin S or C
Microangiopathic hemolytic anemia
2. Hyporegenerative normocytic anemias (inadequate
Anemia of chronic disease
Anemia of chronic renal failure
*Drugs and other substances that have caused aplastic anemia include
amphotericin sulfonamides phenacetin trimethadione
silver chlordiazepoxide tolbutamide thiouracil
carbamazepine chloramphenicol tetracycline oxyphenbutazone
arsenicals chlorpromazine pyrimethamine carbimazole
acetazolamide colchicine penicillin aspirin
mephenytoin bismuth promazine quinacrine
methimazole chlorothiazide dinitrophenol ristocetin
indomethacin phenytoin gold trifluoperazine
carbutamide perchlorate chlorpheniramine streptomycin
phenylbutazone primidone mercury meprobamate
chlorpropamide thiocyanate tripelennamine benzene
The drugs listed above produce marrow aplasia via an unpredictable,
idiosyncratic host response in a small minority of patients. In
addition, many antineoplastic drugs produce predictable, dose-related
marrow suppression; these are not detailed here.
Polycythemia is defined as an increase in total body erythrocyte mass.
As opposed to the situation with anemias, the physician may directly
measure rbc mass using radiolabeling by 51chromium, so as to
differentiate polycythemia (absolute erythrocytosis, as seen in
polycythemia vera, chronic hypoxia, smoker's polycythemia, ectopic
erythropoietin production, methemoglobinemia, and high O2 affinity
hemoglobins) from relative erythrocytosis (as seen in stress
polycythemia and dehydration). Further details of the work-up of
polycythemias are beyond the scope of this monograph.
RDW (Red cell Distribution Width)
The red cell distribution width is a numerical expression which
correlates with the degree of anisocytosis (variation in volume
of the population of red cells). Some investigators feel that it
is useful in differentiating thalassemia from iron deficiency
anemia, but its use in this regard is far from universal
acceptance. The RDW may also be useful in monitoring the results
of hematinic therapy for iron-deficiency or megaloblastic
anemias. As the patient's new, normally-sized cells are
produced, the RDW initially increases, but then decreases as the
normal cell population gains the majority.
Thrombocytosis is seen in many inflammatory disorders and
myeloproliferative states, as well as in acute or chronic blood
loss, hemolytic anemias, carcinomatosis, status
post-splenectomy, post- exercise, etc.
Thrombocytopenia is divided pathophysiologically into
production defects and consumption defects based on examination
of the bone marrow aspirate or biopsy for the presence of
megakaryocytes. Production defects are seen in Wiskott-Aldritch
syndrome, May-Hegglin anomaly, Bernard-Soulier syndrome,
Chediak-Higashi anomaly, Fanconi's syndrome, aplastic anemia
(see list of drugs, above), marrow replacement, megaloblastic
and severe iron deficiency anemias, uremia, etc. Consumption
defects are seen in autoimmune thrombocytopenias (including ITP
and systemic lupus), DIC, TTP, congenital hemangiomas,
hypersplenism, following massive hemorrhage, and in many severe
WBC (White Blood Cell) COUNT
The WBC is really a nonparameter, since it simply represents the
sum of the counts of granulocytes, lymphocytes, and monocytes
per unit volume of whole blood. Automated counters do not
distinguish bands from segs; however, it has been shown that if
all other hematologic parameters are within normal limits, such
a distinction is rarely important. Also, even in the best hands,
trying to reliably distinguish bands from segs under the
microscope is fraught with reproducibility problems. Discussion
concerning a patient's band count probably carries no more
scientific weight than a medieval theological argument.
Granulocytes include neutrophils (bands and segs), eosinophils,
and basophils. In evaluating numerical aberrations of these
cells (and of any other leukocytes), one should first determine
the absolute count by multiplying the per cent value by the
total WBC count. For instance, 2% basophils in a WBC of 6,000/uL
gives 120 basophils, which is normal. However, 2% basophils in a
WBC of 75,000/uL gives 1500 basophils/uL, which is grossly
abnormal and establishes the diagnosis of chronic myelogenous
leukemia over that of leukemoid reaction with fairly good
Neutrophilia is seen in any acute insult to the body,
whether infectious or not. Marked neutrophilia
(>25,000/uL) brings up the problem of hematologic
malignancy (leukemia, myelofibrosis) versus reactive
leukocytosis, including "leukemoid reactions." Laboratory
work-up of this problem may include expert review of the
peripheral smear, leukocyte alkaline phosphatase, and
cytogenetic analysis of peripheral blood or marrow
granulocytes. Without cytogenetic analysis, bone marrrow
aspiration and biopsy is of limited value and will not by
itself establish the diagnosis of chronic myelocytic
leukemia versus leukemoid reaction.
Smokers tend to have higher granulocyte counts than
nonsmokers. The usual increment in total wbc count is
1000/uL for each pack per day smoked.
Repeated excess of "bands" in a differential count of a
healthy patient should alert the physician to the
possibility of Pelger-Huet anomaly, the diagnosis of
which can be established by expert review of the
peripheral smear. The manual band count is so poorly
reproducible among observers that it is widely considered
a worthless test. A more reproducible hematologic
criterion for acute phase reaction is the presence in the
smear of any younger forms of the neutrophilic line
(metamyelocyte or younger).
Neutropenia may be paradoxically seen in certain
infections, including typhoid fever, brucellosis, viral
illnesses, rickettsioses, and malaria. Other causes
include aplastic anemia (see list of drugs above),
aleukemic acute leukemias, thyroid disorders,
hypopitituitarism, cirrhosis, and Chediak-Higashi
Eosinophilia is seen in allergic disorders and invasive
parasitoses. Other causes include pemphigus, dermatitis
herpetiformis, scarlet fever, acute rheumatic fever,
various myeloproliferative neoplasms, irradiation,
polyarteritis nodosa, rheumatoid arthritis, sarcoidosis,
smoking, tuberculosis, coccidioidomycosis,
idiopathicallly as an inherited trait, and in the
resolution phase of many acute infections.
Eosinopenia is seen in the early phase of acute
insults, such as shock, major pyogenic infections,
trauma, surgery, etc. Drugs producing eosinopenia include
corticosteroids, epinephrine, methysergide, niacin,
niacinamide, and procainamide.
Basophilia, if absolute (see above) and of marked degree
is a great clue to the presence of myeloproliferative
disease as opposed to leukemoid reaction. Other causes of
basophilia include allergic reactions, chickenpox,
ulcerative colitis, myxedema, chronic hemolytic anemias,
Hodgkin's disease, and status post-splenectomy.
Estrogens, antithyroid drugs, and desipramine may also
Basopenia is not generally a clinical problem.
Lymphocytosis is seen in infectious mononucleosis, viral
hepatitis, cytomegalovirus infection, other viral infections,
pertussis, toxoplasmosis, brucellosis, TB, syphilis, lymphocytic
leukemias, and lead, carbon disulfide, tetrachloroethane, and
arsenical poisonings. A mature lymphocyte count >7,000/uL is an
individual over 50 years of age is highly suggestive of chronic
lymphocytic leukemia (CLL). Drugs increasing the lymphocyte
count include aminosalicyclic acid, griseofulvin, haloperidol,
levodopa, niacinamide, phenytoin, and mephenytoin.
Lymphopenia is characteristic of AIDS. It is also seen in
acute infections, Hodgkin's disease, systemic lupus, renal
failure, carcinomatosis, and with administration of
corticosteroids, lithium, mechlorethamine, methysergide, niacin,
and ionizing irradiation. Of all hematopoietic cells lymphocytes
are the most sensitive to whole-body irradiation, and their
count is the first to fall in radiation sickness.
Monocytosis is seen in the recovery phase of many acute
infections. It is also seen in diseases characterized by chronic
granulomatous inflammation (TB, syphilis, brucellosis, Crohn's
disease, and sarcoidosis), ulcerative colitis, systemic lupus,
rheumatoid arthritis, polyarteritis nodosa, and many hematologic
neoplasms. Poisoning by carbon disulfide, phosphorus, and
tetrachloroethane, as well as administration of griseofulvin,
haloperidol, and methsuximide, may cause monocytosis.
Monocytopenia is generally not a clinical problem.
Tietz, Norbert W., Clinical Guide to Laboratory Tests,
Friedman, RB, et al., Effects of Diseases on Clinical
Laboratory Tests, American Association of Clinical Chemistry,
Anderson, KM, et al., Cholesterol and Mortality, JAMA 257:
Many thanks to Michael Gayler, FIBMS, DMS, CertHSm (MLSO2, Department
of Chemical Pathology, Leicester Royal Infirmary)
<firstname.lastname@example.org> for the excellent review and comments, and for
the labor of translating American to SI units.
Please send all constructive comments regarding this FAQ to Ed Uthman,
MD <email@example.com>. I am especially interested in correcting any
errors of commission or omission.
This article is provided "as is" without any express or implied
warranties. While reasonable effort has been made to ensure the
accuracy of the information, the author assumes no responsibility for
errors or omissions, or for damages resulting from use of the
Copyright (c) 1994-97, Edward O. Uthman. This material may be reformatted
and/or freely distributed via online services or other media, as long as
it is not substantively altered. Authors, educators, and others are
welcome to use any ideas presented herein, but I would ask for
acknowledgment in any published work derived therefrom. Commercial use
is not allowed without the prior written consent of the author.
version 2.1, 9/10/97