Laboratory testing of patients

with systemic conditions in

periodontal practice
Angelo Mariotti
A principal factor in the etiology of periodontal dis-
ease is the presence of bacterial plaque; however, the
severity of the disease, the type of disease and the
progression of the disease may be dependent on
systemic factors. Although periodontal manifesta-
tions involving systemic factors have been well docu-
mented in the literature, the periodontist's diagnosis
of these conditions is a complicated matter. To pro-
vide a denitive diagnosis, one must have a thorough
understanding of the pathophysiology of disease pro-
cesses as well as a comprehensive history and sys-
tematic physical examination of the patient coupled
with objective data.
Diagnosis, the identication of a disease by careful
investigation of the patient's signs, symptoms and
history, is often a matter of making choices in the
face of uncertainty. Data gathering is the rst step in
the diagnostic process and the medical and dental
history play an extremely important role in collection
of data. It has been estimated that 70% of diagnoses
are established on the basis of patient histories and
greater than 90% are determined on the basis of
history and physical examination (5). Taking an
accurate history is a skill that requires objectivity,
collection of detailed and explicit information, iden-
tication of signs and symptoms of illness versus
wellness and the ability to reproducibly gather infor-
mation (4). Once data from the history and physical
have been collected, the information must be
weighed according to its importance and this can
only be done if the practitioner has the appropriate
knowledge base to distinguish crucial clues.
Although data obtained from a carefully crafted
history and physical examination will most often
be satisfactory for forming a diagnosis, there are
times when more information is required through
the use of diagnostic tests. In other words, clinical
and/or laboratory data must be used to distinguish
between different diagnoses to ascertain the correct
choice. In addition to the diagnosis, laboratory tests
are also extremely important in assisting in the man-
agement of the patient during treatment of the dis-
ease. Therefore, the key to using laboratory tests lies
in the selection of the appropriate test(s), knowing
factual information about the strengths and weak-
nesses regarding the test(s) and selecting the most
useful data to distinguish the critical clues for a spe-
cic diagnostic or treatment choice.
It is not the intent of this manuscript to provide an
extensive review for every laboratory test available for
use to the health care community. It would be
beyond the scope of this article and would not focus
on issues pertinent to the periodontal community.
Therefore, this document will review, evaluate and
provide reference ranges for a variety of laboratory
tests that are typically used by the practicing period-
ontist. If interested, a more comprehensive review of
clinical laboratory tests can be obtained from the
Textbook of Clinical Chemistry (32).
Basic principles for laboratory tests
Laboratory tests can be used to screen for disease in
asymptomatic individuals, to establish or exclude the
presence of a disease in symptomatic patients and to
assist the practitioner in the management of the
patient (e.g. evaluate disease severity, monitor the
progression of the disease, selection of appropriate
drugs, etc.). When selecting a laboratory test, several
important factors will determine the usefulness and
appropriateness of the test in question (see Table 1).
The rst step to consider in laboratory testing is
the collection of the sample from the patient (32).
84
Periodontology 2000, Vol. 34, 2004, 84108 Copyright
#
Blackwell Munksgaard 2004
Printed in Denmark. All rights reserved
PERIODONTOLOGY 2000
Depending on the test, specimen collection may
require very specic techniques or approaches. For
example, fasting may be required prior to collection
of blood samples and excessive shaking of the sam-
ple can cause hemolysis and invalidate the test.
Moreover, the collection of samples for any test has
procedures that must be carefully followed. Further,
specimen collection that is painful or requires multi-
ple sampling for procurement may discourage
patient acceptance. Once the specimen is collected,
patient identication and specimen labeling must be
accurately recorded.
Upon completion of the laboratory test, evaluation
of the results will depend on several test features.
Test accuracy and precision (see Fig. 1) must be good
enough to distinguish changes in patient status from
analytical variation in the test (13). Although the
reference range for an accurate and precise test
hypothetically represents values that are found in
the majority of the population, laboratory results that
are slightly beyond the reference range for an indi-
vidual may represent that small portion of the popu-
lation that is actually healthy (24). Therefore, values
just outside of the reference range for any individual
should be critically evaluated since they may not
represent disease. In addition, it is important to
choose the correct reference values because ranges
can vary depending on age, weight, sex, diet, activity
status, time of day or posture. Interfering factors
must also be considered when evaluating results.
Since exogenous or endogenous factors can interfere
with test results, caution should be used when inter-
preting the results until all extenuating factors are
eliminated (13). The sensitivity and specicity are
also important measures of test performance (22)
(see Fig. 2). A highly sensitive test will identify those
patients who have the disease, whereas a highly spe-
cic test will identify healthy individuals. Laboratory
Fig. 1. The relationship between accuracy and precision
for laboratory tests. Each line represents values from 0 to
100. The red area represents the actual value of the
substance being tested. Line A represents inaccuracy and
imprecision. Repeated measurements ( ) vary and the
results do not represent the true value. Line B represents a
precise but inaccurate test. Repeated measurements exhi-
bit similar results but do not represent the actual value.
Line C is both accurate and precise since repeated mea-
sures are similar and represent the true value.
Table 1. Important characteristics of a laboratory test
Characteristic Description
Accuracy Assesses a value that is in accordance with the actual or true quantity found in the patient
Cost Expense can affect patient acceptance
Interfering Factors Endogenous (e.g. abnormal physiologic states) or exogenous (e.g. drug usage) elements
that can alter test results
Morbidity Discomfort associated with a test can affect patient compliance
Precision Reproducibility of test
Reference Range The limits of the test result that represent values found in 95% of the population
Sensitivity The probability that a patient with the disease has a positive test
Specificity The probability that a healthy patient has a negative test
Specimen collection Gathering a specimen from the patient at the appropriate time
0 100
0
100
0 100
(A)
(B)
(C)
Laboratory testing of systemic conditions
85
tests may be highly sensitive or specic, but rarely
both. This forces the clinician to make difcult deci-
sions since a highly sensitive test with poor speci-
city will contain many false-negatives and will not be
able to adequately identify healthy individuals. Con-
versely, a highly specic test with low sensitivity will
contain a high number of false positives and will not
be able to adequately identify individuals who are
diseased. Finally, the cost of the test can affect
patient acceptance, especially when such tests have
modest specicity or sensitivity. For any laboratory
test, the practical benets of a test must always be
weighed against the potential disadvantages to the
patient.
Periodontal epistemology for
laboratory tests
Can a periodontist order a soluble amyloid b-protein
test to determine if Alzheimer's disease is the reason
why the patient continually forgets to brush their
teeth? As a health care professional, most jurisdic-
tions give the periodontist the opportunity to diag-
nose any systemic disease or condition; however,
realistically there are limits to what can or should
be done. Diagnostic tests can provide powerful evi-
dence for the presence of a particular disease and
allow the practitioner to pursue a rational course of
treatment. For example, recalcitrant forms of period-
ontal disease may respond more favorably to treat-
ment once systemic issues have been addressed. A
case in point involves diabetic patients. It is well
recognized that successful treatment of the patient
with diabetes mellitus requires control of blood glu-
cose levels (16). On the other hand, ordering a
laboratory test to identify whether a patient is preg-
nant (especially when she desires not to know, let
alone be) may not be the most appropriate action to
consider in the treatment of periodontal diseases. In
other words, there is little to prevent you from order-
ing a laboratory test but there may be a thousand
reasons to consider other options. To be sure, there
are no rules or regulations to dictate your actions;
however, there are a number of factors to consider.
Laboratory tests should be ordered as a result of
suspicious oral ndings or if aspects of your treat-
ment can potentially affect the systemic health of
the patient.
Histories and physical examinations are power-
ful instruments for diagnosis but sometimes
laboratory tests are necessary to conrm if the
patient has a systemic illness. Further, arranging
to have a laboratory test for further information to
assist you in the management of the patient is
appropriate. On the other hand, the casual order-
ing of any test in an effort to screen for disease
without clinical ndings is inappropriate.
The strengths and weaknesses of the test should be
known and the results must be accurately inter-
preted.
The person who orders the test is responsible for
requesting the correct test and then accurately
interpreting the result. This means that the data
should be useful in helping to distinguish critical
clues to make a diagnosis or to develop a thera-
peutic treatment choice. Therefore, knowledge of
the strengths and weaknesses of any test that is
ordered is essential.
The nancial costs to patients and to your practice
should be carefully considered.
The doctor-patient relationship has evolved dra-
matically because of two signicant factors: 1) the
increasing cost of technology for health care and 2)
the inuence of third-party payers otherwise
known as insurance companies. Laboratory tests
are expensive not only to the patient but also to the
practitioner. Patients may be hesitant to pay for
out-of-pocket expenses that are not covered by
dental or medical insurance. Unfortunately, peri-
odontists sometimes nds themselves between the
patient and the insurance carrier when trying to
prescribe treatment. The type of insurance (health
maintenance organization vs. preferred provider
organization vs. point-of-service plans vs. physi-
cian hospital organization vs. Medicare vs. Medi-
caid vs. dental insurance vs. medical insurance vs.
other insurance systems) will determine whether
the test is paid for as well as if the periodontist is
compensated for collection of the specimen. At
this time, dental insurance policies rarely cover
laboratory tests while some medical policies may
not recognize dentists who order the laboratory
tests.
DISEASE
Present Absent
TP True False
Sensitivity = ----------- Positive Positive Positive
TP+FN (TP) (FN)
TEST
TN False True
Specificty = ------------- Negative Negative Negative
TN+FP
(FN) (TN)
Fig. 2. Calculation of sensitivity and specicity.
86
Mariotti
Privileges for writing laboratory tests may vary.
Consequently the periodontist must have privi-
leges at the laboratory where they are ordering the
test and must knowhowto write the order correctly.
Types of laboratory tests
Bone studies
Osteomyelitis
Osteomyelitis is inammation of bone and bone
marrow that is often associated with a bacterial
infection. The response to the infection can either
be acute or chronic depending on the extent of the
infection and the resistance of the patient. Chronic
forms of osteomyelitis may be asymptomatic for
years. Osteomyelitis can occur in otherwise healthy
individuals but certain patients, like those under-
going radiation therapy, may be more susceptible.
More specically, patients receiving a large dose of
radiation (>6000 cGy) to the jaws often develop
osteoradionecrosis, an area of bone which undergoes
conversion to a hypovascular, hypocellular and
hypoxic alveolar tissue with diminished repair and
remodeling capacity.
Laboratory tests (17)
Radiopharmaceutical scintigraphy. After IV injec-
tion of a radiopharmaceutical (technetium [
99m
Tc] ,
gallium [
67
Ga] , indium [
111
In]), the mandible or max-
illa is scrutinized by single photon emission com-
puted tomography (SPECT) to determine areas of
abnormally increased uptake of the radiopharma-
ceutical. After IV injection, technetium is taken up
by bone cells and gallium will concentrate in white
blood cells. When indium is used, white blood cells
are collected, labeled with radioactive indium and
returned to the blood stream. Areas with increased
uptake or cellular localization usually designate areas
of infection. Positive interpretation of technetium
scans can also include bone fractures, bone necrosis,
bone tumors, degenerative arthritis, Paget's disease
or renal osteodystrophy. Positive interpretation of
gallium and indium scans can also indicate acalcu-
lous cholecystitis, acute cholecystitis, chronic chole-
cystitis, common bile duct obstruction or cystic
duct syndrome. Often radiopharmaceutical scans
are combined (
99m
Tc &
67
Ga or
99m
Tc &
111
In or
67
Ga &
111
In) to increase the sensitivity of the test
for osteomyelitis.
Endocrine studies
Diabetes mellitus
Diabetes mellitus is a chronic disease characterized
by disorders of insulin production or resistance to
insulin that results in alterations in metabolism of
carbohydrate, fat and protein (27). Diabetes mellitus
most commonly appears as one of two recognized
clinical forms: type 1 and type 2. The onset of type 1
diabetes generally occurs prior to 30 years of age and
the individual requires exogenous insulin treatment
with dietary management to achieve control of blood
glucose levels (10, 27). The onset of type 2 diabetes
usually occurs in obese individuals after the age of 40
and often is treated with exercise, diet and antidia-
betic drugs or exogenous insulin (10, 27). In the Uni-
ted States, diabetes mellitus is thought to affect
approximately 8% of the population.
Laboratory tests (10, 27)
Blood glucose levels are carefully controlled in the
human body by a number of hormones including
insulin, glucagon, adrenocorticosteroids, adrenocor-
ticotropic hormone, epinephrine and thyroxine.
When glucose levels increase in the blood, insulin
is released from the beta cells of pancreatic islets
to decrease plasma levels of glucose. In general, true
glucose elevations indicate diabetes mellitus. There-
fore, a blood glucose test, which is a direct measure-
ment of blood glucose levels, is commonly used to
determine if a patient is diabetic.
Types of blood glucose tests (see Table 2): Fasting
blood glucose. The patient must fast for at least 8 h
and no more than 16 h prior to the blood draw and
test.
Glucose tolerance test. After a 12-h fast, the patient
is instructed to consume a 75 mg oral bolus of dex-
trose. Prior to ingestion as well as 1 h and 2 h follow-
ing oral ingestion, blood glucose levels are
determined.
In nonpregnant patients, two of the following
observations are required to diagnose diabetes mel-
litus. They may be the same two observations or any
combination of observations and both observations
should be separated by 24 h. These observations
include:
fasting blood glucose levels greater than 126 mg/dl.
symptoms of uncontrolled diabetes and a random
blood glucose level greater than or equal to
200 mg/dl.
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Laboratory testing of systemic conditions
Table 2. Diabetes mellitus (17, 28, 30)
Test Reference values Endogenous interfering
factors
Exogenous interfering factors Interpretation
Fasting
Plasma
Glucose
Normal Range: (70100 mg/dl);
Values of >126 mg/dl on more than
one occasion are diagnostic
for diabetes mellitus. Hypoglycemia
defined as <50 mg/dl (men)
or <40 mg/dl (women).
Stress (trauma,
infection, burns, etc.)
Increased glucose levels with
caffeine, antidepressants,
b-adrenergic blocking agents,
corticosteroids, dextrothyroxine,
diazoxide, diuretics, epinephrine,
estrogens, glucagon, isoniazid,
lithium, phenothiazines, phenytoin,
salicylates, and triamterene.
Decreased glucose levels with
acetaminophen, alcohol, anabolic
steroids, clofibrate, disopyramide,
gemfibrozil, insulin, monoamine
oxidase inhibitors, pentamide,
propranolol, tolazamide, and
tolbutamide.
Increased levels in
acromegaly, acute pancreatitis, chronic renal
failure, Cushing's syndrome,
diabetes mellitus, glucagonoma,
and pheochromocytoma. Decreased
levels in Addison's disease, extensive
liver disease, hypopituitarism,
hypothyroidism, insulinoma, and
starvation.
Glucose
tolerance
test
Fasting: <105 mg/dl;
1 hour: <190 mg/dl; 2 hour:
<165 mg/dl; 3 hour: <145 dl/mg
Smoking, stress, exercise,
fasting prior to the
glucose tolerance test
Drugs that cause glucose intolerance
include antihypertensives,
anti-inflammatory drugs, b blockers,
furosemide, nicotine,
oral contraceptives, phenothiazides,
psychiatric drugs, steroids
and thiazide diuretics.
Increased with acute pancreatitis,
acute stress, acromegaly, chronic
renal failure, Cushing's syndrome,
diabetes mellitus, glucagonoma,
myxedema, and pheochromocytoma.
Glycosylated
hemoglobin
Good diabetic control 2.55.9%;
fair diabetic control 68%; poor
diabetic control >8%.
Values will vary according to
laboratory methods.
Hemoglobinopathies Increased levels with acromegaly,
corticosteroid therapy, Cushing's
disease, glucagonoma,
pheochromocytoma, pregnancy,
and splenectomy.
Decreased levels with chronic blood
loss, chronic renal failure and
hemolytic anemia.
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blood glucose levels greater than 190 mg/dl 1 h
and/or greater than 165 mg/dl 2 h following inges-
tion of a 75 g bolus of oral dextrose.
Glycosylated hemoglobin (see Table 2) is not used
to diagnose diabetes but is used to monitor diabetic
treatment by providing a long-term index of the aver-
age blood glucose level. As the red blood cell circu-
lates, glucose combines with a type of hemoglobin
designated as hemoglobin A
1
(HbA
1
). Since the
amount of glycosylation of HbA
1
depends on the
amount of glucose in the blood stream over the life-
span of a red blood cell, it reects the average blood
sugar level over a 100120-day lifespan. Although
values may vary depending on laboratory methods,
patients with a value greater than 8% are considered
to have poor diabetic control.
Pregnancy
After fertilization of the ovum, the placental tropho-
blast secretes human chorionic gonadotropin (HCG).
This hormone can be detected as early as 10 days
following conception. All pregnancy tests are based
on the detection of HCG. Methods of detecting preg-
nancy in women use bioassays, agglutination tests
and immunoassays (19). All modern techniques use
immunoassays. Qualitative tests using urine can
easily detect pregnancy; however, the advantage of
qualitative serum tests is that they can detect preg-
nancy at an earlier date than when HCG is extracted
from urine. Quantitative pregnancy tests that use
blood are primarily employed to determine the prog-
nosis of early pregnancy. Women taking diuretics
and promethazine may have false negatives with
these tests, whereas women taking anticonvulsants,
antiparkinsonian drugs, hypnotics and tranquillizers
may have false-positive results. Although you may
never order a pregnancy test professionally, there
will be patients in your practice who are interested
in starting a family or who ``think'' that they are
pregnant. A brief overview of the laboratory tests will
allow you to understand the tests that are currently
available.
Laboratory tests (1, 31)
Bioassays. Urine from patient is injected into an
animal to determine if there is stimulation of
reproductive system. For example, stimulation of
the corpus luteum in the ovaries of immature
mice would indicate HCG being present and
would be diagnostic of pregnancy. This test
requires the subject to be at least 6 weeks into her
pregnancy.
Agglutination inhibition tests. The presence of HCG
in the sample prevents agglutination of CG-coated
latex particles and designates pregnancy. This test is
used for qualitative detection of HCG.
Immunologic tests. This test determines the pre-
sence of HCG using antibodies. Early tests, which
used the whole HCG molecule, were prone to have
false-positives and usually required the subject to be
at least 4 weeks into her pregnancy. More recent tests
have used the b-subunit of HCG to improve test
sensitivity and reduce the time necessary after con-
ception (37 days) to detect the presence of HCG.
These tests can use urine or blood and require 5 min
to 2 h to perform.
Radioimmunoassay. This test requires a blood
or urine sample to measure the b-subunit of HCG
and is extremely sensitive. The test can be acco-
mplished in 15 h and is done in the hospital
laboratory.
Hematologic studies
Anemias
Anemias are distinguished by reduced hemoglobin
levels (7). Common features leading to low hemoglo-
bin levels include congenital or acquired defects that
cause suppression of hematopoiesis or erythropoi-
esis, drugs, toxins, metabolic abnormalities, vitamin
deciencies, excessive blood loss, defective red blood
cells and abnormal proliferation of bone marrow
elements. Anemias that are the result of alterations
of red blood cells can be categorized as normocytic,
normochromic anemias (e.g. chronic illness, acute
blood loss, aplastic anemia, acquired hemolytic ane-
mias), microcytic, hypochromic anemias (e.g. iron
deciency, thalassemia, lead poisoning), microcytic,
normochromic anemia (e.g. renal disease) and
macrocytic, normochromic anemias (e.g. vitamin
B
12
or folic acid deciency, hydantoin ingestion, che-
motherapy).
Laboratory tests (11) (see Table 3)
Ferritin. This is a sensitive test to determine iron-
deciency anemia. A ferritin level below 10 mg/dl is
diagnostic of iron deciency anemia.
Folic acid. This test is used to ascertain if patients
have megaloblastic anemia or to assess the nutri-
tional status of alcoholics.
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Laboratory testing of systemic conditions
Table 3. Anemia (17, 28, 30)
Test Reference values Endogenous interfering
factors
Exogenous interfering factors Interpretation
Ferritin Normal range:
Male: 12300 ng/ml;
Female: 10150 ng/ml;
Anemia defined as
<10 mg/dl
Hemolytic diseases,
excessive iron
storage disorders
Recent transfusion Increased levels associated with
advanced cancers, alcoholism,
hemochromatosis, hemolytic anemia,
hemosiderosis, inflammatory disease,
and megaloblastic anemia. Decreased
levels with hemodialysis,
iron-deficiency anemia, and severe
protein deficiency.
Folic Acid Normal range:
525 ng/ml
Folic acid decreases with
alcohol, aminopterin,
aminosalicylic acid,
ampicillin, antimalarials,
chloramphenicol,
erythromycin,
estrogens, methotrexate, oral
contraceptives, penicillin,
phenobarbital, phenytoin,
and tetracyclines.
Increased levels with pernicious anemia,
recent massive blood infusion and
vegetarianism. Decreased levels with
chronic renal disease, hemolytic anemia,
liver disease, megaloblastic anemia,
malabsorption, malignancy, malnutrition,
and pregnancy.
Hematocrit Normal range:
Male: 42%52%;
Female 37%47%;
Values <15% or >60%
should be viewed
carefully.
Abnormal red blood cell
size, elevated white blood
cell counts, hemodilution,
pregnancy, living at high
altitudes
Hematocrit may be decreased
with chloramphenicol
and penicillin.
Increased levels with congenital heart
disease, erythrocytosis, polycythemia
vera, severe chronic obstructive
pulmonary disease, and severe
dehydration. Decreased levels with
anemia, cirrhosis, dietary deficiency,
hemoglobinopathy, hemolytic anemia,
and hemorrhage.
Hemoglobin Normal range:
Male: 1418g/dl;
Female: 1216 g/dl;
Values <5 g/dl or > 20 g/dl
should be viewed carefully.
Pregnancy, diurnal variation
(highest at 8 am and lowest
at 8 pm), smoking, living
at high altitude
Hemoglobin increased with
gentamicin and methyldopa.
Hemoglobin decreased with
antibiotics, antineoplastic drugs,
aspirin, indomethacin, rifampin
and sulfonamides.
Increased levels with chronic obstructive
pulmonary disease, congenital heart
disease, erythrocytosis, severe dehydration,
and severe polycythemia vera. Decreased
levels with anemia, bone marrow failure,
cirrhosis, dietary deficiency, Hodgkin's
disease, hemoglobinopathy, hemolytic
anemia, hemorrhage, leukemia, lymphoma,
multiple myeloma, pregnancy, prosthetic
valves, renal disease, and rheumatoid/
collagen vascular diseases.
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Iron Normal range:
Iron: Male: 80180 mg/dl;
Female: 60160 mg/dl;
TIBC: 240-460 mg/dl
Transferrin: Male: 215365 mg/dl;
Female: 250380 mg/dl
Hemolytic diseases Iron levels increased with
chloramphenicol, dextran,
estrogens, ethanol, iron
preparations, methyldopa, oral
contraceptives, recent blood
transfusions, and recent
ingestion of high iron meal.
Iron levels decreased with
adrenocorticotropic hormone,
chlolestyramine, chloramphenicol,
colchicines, deferoxamine,
methicillin and testosterone.
Increased with hemochromatosis,
hemolytic anemia, hemosiderosis,
hepatic necrosis, hepatitis, iron
poisoning, lead toxicity, and massive
blood transfusion. Decreased with
chronic blood loss, inadequate internal
absorption of iron, insufficient
dietary iron, iron deficiency anemia,
pregnancy, and neoplasia.
RBC Count Normal range:
Male: 4.76.1 million/ml;
Female: 4.25.4 million/ml
RBC counts decrease
during pregnancy. RBC
counts increase when
living at high altitude.
Hydration can decrease
RBC counts whereas
dehydration can increase
RBC counts.
Red blood cells increase
with gentamicin and methyldopa.
Red blood cells decrease
with chloramphenicol,
hydantoins and quinidine.
Increased levels with congenital heart
disease, erythrocytosis, hemoglobinopathies
polycythemia vera, pulmonary disease,
severe dehydration and severe chronic
obstructive pulmonary disease. Decreased
levels with anemia, bone marrow failure,
cirrhosis, dietary deficiency, leukemia,
lymphoma, multiple myeloma,
hemoglobinopathy, hemolytic anemia,
hemorrhage, Hodgkin's disease, pregnancy,
prosthetic valves, renal disease, and
rheumatoid/collagen-vascular diseases.
Schilling test Normal range: 840%
excretion of radioactive
vitamin B
12
within 24 h
Renal insufficiency, diabetes,
hypothyroidism may
cause reduced
excretion of radioactive
vitamin B
12
.
Laxatives and inadequate
collection of urine could
decrease the rate of
vitamin B
12
absorption.
Decreased levels with hypothyroidism,
intestinal malabsorption, liver disease,
and pernicious anemia.
Vitamin B
12
Normal range:
160950 pg/ml
Vitamin B
12
increases with
chloral hydrate.
Vitamin B
12
decreases with
alcohol, aminoglycosides,
aminosalicylic acid,
anticonvulsants, colchicine,
and oral contraceptives.
Increased with leukemia, myeloproliferative
disease, polycythemia vera, and severe liver
dysfunction. Decreased levels with
achlorhydria, atrophic gastritis, folic acid
deficiency, intestinal worm infestation, large
proximal gastrectomy, pernicious anemia,
malabsorption syndromes, pregnancy, resection
of terminal ileum, vitamin C deficiency, and
Zollinger-Ellison syndrome.
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Hematocrit. A rapid and indirect measurement of
red blood cell number and volume. It is an integral
component of the evaluation of anemic patients.
Hemoglobin. Although hemoglobin is measured,
this is a rapid and indirect measure of red blood cell
count. It is an integral component of the evaluation
of anemic patients.
Iron. This test is used to evaluate iron metabolism
in patients and deciencies may indicate an anemia.
Decreased serum iron, elevated TIBC (plasma pro-
tein that carries iron) and low transferrin values are
indicative of iron deciency anemia.
Red blood cell count. This measures the amount of
red blood cells and is and integral component of the
evaluation of anemic patients.
Schilling test. This test is performed to detect vita-
min B
12
absorption in patients with pernicious ane-
mia. Urinary levels of radioactive vitamin B
12
are
evaluated at two stages. Patients who lack intrinsic
factor will have abnormal results in stage one and
normal results for stage two, whereas malabsorption
from the intestines will have abnormal results from
both stage one and stage two.
Vitamin B
12
. This test measures the amount of vita-
min B
12
in the blood and can be used to evaluate
patients who have megaloblastic anemia or who are
malnourished.
Clotting disorders
Hemostasis consists of a cascade of proteins to pro-
duce a stable clot (18, 21) (see Fig. 3). The rst reac-
tion of the body to stop bleeding is the adherence of
platelets to the blood vessel. Secondary hemostasis
comprises several stages that ultimately will form a
brin clot at the site of vascular injury. The intrinsic
pathway involves factors VIII, IX, XI and XIII, which
form a complex on the connective tissue supporting
endothelial cells. The extrinsic system forms a com-
plex between the tissue factor and factor VII. The
common pathway involves factor X, thrombin and
brin to form a stable clot.
Injury to blood vessel
Platelet aggregation
X Xa
Prothrombin (II) Thrombin (IIa)
Fibrinogen (I) Fibrin (Ia)
Fibrin Stabilizing Factor XIII
Stable Fibrin Clot
XII XIIa
XI XIa
IX IXa
VIII VIIIa
I
n
t
r
i
n
s
i
c

S
y
s
t
e
m
Tissue
Thromboplastin
VII
E
x
t
r
i
n
s
i
c

S
y
s
t
e
m
C
o
m
m
o
n

P
a
t
h
w
a
y
Primary Stage
Fig. 3. Hemostasis cascade of coagulation factors.
92
Mariotti
Table 4. Coagulation (17, 28, 30)
Test Reference values Endogenous
interfering
factors
Exogenous interfering
factors
Interpretation
Bleeding time
(Ivy)
Normal range:
19 min;
Values >15 min
on repeated
evaluations
should be
carefully
considered.
Extremes in
body
temperature
Prolonged bleeding
times with alcohol,
anticoagulants, dextran,
indomethacin,
salicylates, streptokinase,
allopurinol, antibiotics,
halothane, nonsteroidal
anti-inflammatory drugs,
urokinase, and warfarin.
Prolonged values with
Bernard-Soulier
syndrome, bone marrow
failure, capillary fragility
abnormalities,
collagen vascular disease,
connective tissue disorder,
Cushing's disease,
disseminated
intravascular coagulation,
Glanzmann's uremia,
Henoch-Schonlein
syndrome, hypersplenism,
leukemia, purpuras,
severe liver
disease, telangiectasia,
thrombocytopenia,
thromboasthenia, tumor
infiltration of bone marrow,
and von Willebrand's disease.
Partial
thromboplastin
time
Normal range:
6070 seconds.
Desired range of
anticoagulant
therapy is
1.52.5 times the
control values.
Prolonged partial
thromboplastin time
with antihistamines,
ascorbic acid,
chlorpromazine, heparin
and salicylates.
Prolonged levels with
cirrhosis, coumarin
administration, congenital
clotting factor deficiencies
(e.g. von Willebrand's
disease, hemophilia,
hypofibrinogenemia),
disseminated intravascular
coagulation, heparin
administration and
vitamin K deficiency.
Delayed levels with early
stages of disseminated
intravascular coagulation
and extensive cancer.
Platelet
count
Normal range: Adult:
150,000400,000/mm
3
;
Values <50,000/mm
3
or >1,000,000/ mm
3
should be carefully
considered.
Living at
high
altitudes,
menstruation
Platelet levels increase
with estrogens and
oral contraceptives.
Platelet levels decrease
with acetaminophen,
aspirin, chemotherapeutic
agents, chloramphenicol,
colchicines, H
2
-blocking a
gents, hydralazine,
indomethacin, isoniazid,
quinidine, streptomycin,
sulfonamides, thiazide
diuretics, and tolbutamine.
Increased levels with
iron-deficiency
anemia, malignant disorders
(e.g. leukemia, lymphoma,
solid colon tumors),
polycythemia vera,
postsplenectomy syndrome,
and rheumatoid arthritis.
Decreased levels with
cancer chemotherapy,
disseminated intravascular
coagulation, erythematosus,
Graves's disease, hemolytic
anemia, hemorrhage,
hypersplenism, immune
thrombocytopenia,
leukemia, infection,
pernicious anemia, systemic
lupus, and thrombotic
thrombocytopenia.
93
Laboratory testing of systemic conditions
Laboratory tests (8) (see Table 4)
Bleeding time. When vascular injury occurs, plate-
lets must adhere to the contracting vessel wall to
activate hemostasis. If the quantity or quality of
platelets is inadequate or if the vascular contrac-
tion is insufcient, then bleeding time will be
affected. A single protracted bleeding time does not
establish an abnormality since variance may be a
result of technical procedures associated with the
test or the possibility of lacerating a large blood
vessel. Therefore results demonstrating extended
bleeding times require repeated tests to ensure accu-
racy. The Ivy bleeding time test is the test most often
used.
Partial thromboplastin time. The secondary stage of
the hemostatic mechanism comprises the intrinsic
and extrinsic system. Partial thromboplastin time is
used to assess the intrinsic system of hemostasis,
which includes factors I (brinogen), II (prothrom-
bin), V, VIII, IX, X, XI and XII. When any of these
factors are insufcient (e.g. hemophilia A or B) or
when heparin is being used, the partial thromboplas-
tin time will be prolonged.
Platelet count. Platelets are small, round nonnu-
cleated cells formed in the bone marrow from mega-
karyocytes whose function is to maintain vascular
integrity. The platelet count is the actual count of the
number of platelets per cubic millimeter of blood.
Prothrombin time. The secondary stage of the
hemostatic mechanism comprises the intrinsic and
extrinsic system. Prothrombin time is used to access
the extrinsic system and common pathway of
hemostasis, which includes factors I (brinogen), II
(prothrombin), V, VII and X. When any of these fac-
tors are insufcient or when a drug that affects these
factors is being used, the prothrombin time will be
prolonged. Standardized prothrombin time results
make use of the international normalized ratio
(INR) value (see Table 5), which takes into considera-
tion the sensitivity of thromboplastin used in the
standard reagent and the type of instrument used
to evaluate the reagent.
Leukemia
Leukemia is a progressive, malignant hematologic
disorder characterized by an abnormal proliferation
and development of leukocytes and precursors of
Table 4. continued
Test Reference values Endogenous
interfering
factors
Exogenous interfering
factors
Interpretation
Prothrombin
time
Normal range:
11.012.4 seconds;
Values >20 seconds
should be carefully
considered.
Diarrhea or
malabsorptive
syndromes
Prolonged prothrombin
times with alcohol,
allopurinol, aminosalicylic
acid, barbiturates, b-lactam
antibiotics, chloral hydrate,
cephalothins,
chloramphenicol,
chlorpromazine,
cholestyramine, cimetidine,
clofibrate, colestipol,
glucagon, heparin,
methyldopa, neomycin,
oral anticoagulants,
propylthiouracil, quinidine,
quinine, salicylates, and
sulfonamides. Shortened
prothrombin times with
anabolic steroids,
barbiturates, chloral hydrate,
digitalis, diphenhydramine,
estrogens, griseofulvin,
oral contraceptives
and vitamin K.
Prolonged levels with bile duct
obstruction, coumarin,
disseminated intravascular
coagulation, hereditary factor
deficiency, liver disease,
massive blood transfusion,
salicylate intoxication, and
vitamin K deficiency.
94
Mariotti
leukocytes in the blood and bone marrow (20). Leu-
kemia is classied on the basis of the duration (acute
or chronic) and the type of cell involved (myeloid or
lymphoid) and the number of cells in the blood (leu-
kemic or aleukemic). The most common forms of
acute leukemias include acute lymphocytic leuke-
mia, characterized by abnormal growth of lympho-
cyte precursors, and acute myelogenous leukemia,
characterized by myeloid precursors. The two com-
mon chronic forms of leukemia include chronic
myelogenous leukemia, characterized by abnormal
growth of granulocytic precursors, and chronic lym-
phocytic leukemia, marked by an uncontrolled
spread of abnormal lymphocytes.
Laboratory tests (20) (see Table 6)
Acute leukemias. Bone marrow aspiration followed
by microscopic examination will show a proliferation
of immature white blood cells for acute leukemias. If
the marrow is free of leukemic cells but the patient
has clinical signs of leukemia, a posterior superior
iliac spine biopsy should be performed. Blood counts
exhibit a thrombocytopenia and neutropenia and a
white blood cell differential determines the cell type.
Chronic myelogenous leukemia. The presence of the
Philadelphia chromosome in peripheral blood or
bone marrow, which is determined by chromosome
karyotyping and low leukocyte alkaline phosphatase
levels, is diagnostic for this disease. Analysis of per-
ipheral blood shows leukocytosis (white blood cell
count >50,000/mm
3
), occasionally a leukopenia
(white blood cell count <5000/mm
3
), neutropenia
(neutrophils <1500/mm
3
) and increased circulating
myeloblasts.
Chronic lymphocytic leukemia. Blood studies reveal
granulocytopenia, neutropenia (<1500/ mm
3
), lym-
phocytosis (>10,000 mm
3
), thrombocytopenia
(<150,000 mm
3
), hemoglobin counts under 11 g/dl,
hypogammaglobulinemia and depressed serum glo-
bulin levels.
Hepatobiliary studies
The liver performs multifaceted and signicant func-
tions related to metabolism of endogenous and exo-
genous agents, detoxication of noxious agents,
metabolism of carbohydrates, synthesis of plasma
proteins, nonessential amino acids and vitamins, sto-
rage of iron and vitamins, secretion of bile and
removal of ammonia from body uids with its con-
version to urea (26).
Laboratory tests (6) (see Table 7)
Alanine aminotransferase. Injury or disease will
cause release of alanine aminotransferase, an
enzyme found primarily in the liver. Hepatocellular
Table 5. Management of patients using the International Normalized Ratio (INR) (23, 25)
Periodontal treatment Safe (INR) Borderline (INR) Adjustment (INR)
Prophylaxis <3.5 3.5
Scaling and root planing <2.5 2.5 to 3.5 >3.5
Extraction <2.5 2.5 to 3.5 >3.5
Gingivoplasty <2.5 2.5 to 3.5 >3.5
Multiple extraction (<4 teeth) <2.5 2.5 to 3.5 >3.5
Gingivectomy <1.5 1.5 to 2.5 >2.5
Minor flap surgery <1.5 1.5 to 2.5 >2.5
Full arch extractions 1.5 1.5
Extensive flap surgery <1.5 1.5
In the safe INR range, treatment can be initiated without altering dose of anticoagulant. The borderline INR requires consultation with a physician to determine
whether anticoagulant needs to be adjusted. The adjustment INR range requires a change in the patient's anticoagulant therapy prior to treatment. These values
can be considered when there are no other risk factors.
Considerable controversy still exists when deciding whether to have patients undergo periodontal treatment concomitantly with an anticoagulant or after the
patient has discontinued coagulant treatment. It has been suggested that patients can proceed with dental treatment without alteration of their oral
anticoagulation therapy as long as they are within prescribed INR levels; however, it has also been suggested that patients with a low risk for systemic
embolization should discontinue oral anticoagulant therapy for several days before minor treatment. For prevention of postoperative bleeding, a topical
antifibrinolytic agent (e.g. tranexamic acid) can be applied.
95
Laboratory testing of systemic conditions
Table 6. Leukemia (17, 28, 30)
Disease Test & reference values Endogenous interfering
factors
Exogenous interfering factors Interpretation
Acute
leukemias
Bone marrow aspiration:
Immature white blood cells in
marrow. White blood cell counts:
thrombocytopenia (<100,000 mm
3
);
neutropenia (<1,500/mm
3
)
Physical activity,
stress, splenectomy
White blood cells counts
increase with allopurinol,
aspirin, chloroform, epinephrine,
heparin, quinine, steroids,
triamterene. White blood
cell counts decrease with
antibiotics, anticonvulsants,
antihistamines, antimetabolites,
antithyroid drugs, arsenicals,
barbiturates, chemotherapeutic
agents, diuretics, sulfonamides.
Altered levels with acquired
immunodeficiency syndrome, acute
hemorrhagic marrow hyperplasia,
agranulocytosis, anemia, chronic
inflammatory disease, Hodgkin's
disease, hypersensitivity states,
infection, leukemia, lymphoma,
multiple myelomas, myelofibrosis,
neoplasm, polycythemia
vera, and rheumatic fever.
Chronic
myelogenous
leukemia
Chromosome karyotyping:
Philadelphia chromosome. White
blood cell counts: leukocytosis
(>50,000/mm
3
), or occasionally a
leukopenia (< 5000/mm
3
),
neutropenia (<1500/mm
3
) increased
circulating myeloblasts (5% or less);
low leukocyte alkaline phosphatase
levels (<40)
Physical activity,
stress, splenectomy
White blood cells counts
increase with allopurinol,
aspirin, chloroform, epinephrine,
heparin, quinine, steroids,
triamterene. White blood
cell counts decrease
with antibiotics, anticonvulsants,
antihistamines, antimetabolites,
antithyroid drugs, arsenicals,
barbiturates, chemotherapeutic
agents, diuretics,
sulfonamides.
Altered levels with acquired
immunodeficiency syndrome, acute
hemorrhagic marrow hyperplasia,
agranulocytosis, anemia, chronic
inflammatory disease, Hodgkin's disease,
hypersensitivity states, leukemia,
lymphoma, multiple myelomas,
myelofibrosis, infection, neoplasm,
polycythemia vera, and rheumatic fever.
Chronic
lymphocytic
leukemia
White blood cell counts:
neutropenia (<1500/mm
3
),
lymphocytosis (>10,000 mm
3
),
thrombocytopenia (<150,000 mm
3
),
hemoglobin counts <11g/dl,
hypogammaglobulinemia depressed
serum globulin levels
Physical activity, stress,
splenectomy
White blood cells counts
increase with allopurinol,
aspirin, chloroform, epinephrine,
heparin, quinine, steroids,
triamterene. White blood
cell counts decrease with
antibiotics, anticonvulsants,
antihistamines, antimetabolites,
antithyroid drugs, arsenicals,
barbiturates, chemotherapeutic
agents, diuretics, sulfonamides.
Altered levels with acquired
immunodeficiency syndrome,
acute hemorrhagic marrow
hyperplasia, agranulocytosis,
anemia, chronic inflammatory
disease, Hodgkin's disease,
hypersensitivity states, infection,
leukemia, lymphoma, multiple
myelomas, myelofibrosis, neoplasm,
polycythemia vera, and rheumatic
fever.
9
6
M
a
r
i
o
t
t
i
Table 7. Hepatobiliary diseases (17, 28, 30)
Test Reference values Endogenous interfering
factors
Exogenous interfering factors Interpretation
Alanine amino-
transferase
Normal range:
Males: 1035 U/l;
Females: 924 U/l
Alanine aminotransferase will increase
with acetaminophen, allopurinol,
aminosalicylic acid, ampicillin,
azathioprine, carbamazepine,
cephalosporins, chlordiazepoxide,
chlorpropamide, clofibrate,
cloxacillin, codeine, dicumarol,
indomethacin, isoniazid, methotrexate,
methyldopa, nafcillin, nalidixic acid,
nitrofurantoin, tetracyclines, and
verapamil.
Significantly increased levels with
hepatic ischemia, hepatic necrosis,
and hepatitis. Moderately increased
levels with cirrhosis, cholestasis,
hepatic tumor, hepatotoxic drugs,
obstructive jaundice, severe burns, and
trauma to striated muscle. Modest
increase in levels with infectious
mononucleosis, myocardial infarction,
myositis, pancreatitis, and shock.
Alkaline
phosphatase
Normal range: Males
19 years: 98251 U/l;
Females 2465 years:
81282 U/l; Females
65 years: 119309 U/l
Alkaline phosphatase increased
with allopurinol, antibiotics,
azathioprine, colchicine, fluorides,
indomethacin, isoniazid, methotrexate,
methyldopa, nicotinic acid,
phenothiazine, probenecid, recent
ingestion of a meal, tetracycline,
and verapamil. Alkaline phosphatase
decreases with arsenicals, cyanides,
fluorides, nitrofurantoin, oxalates,
and zinc salts.
Increased levels with healing fracture,
hyperparathyroidism, intestinal
ischemia or infarction, intrahepatic or
extrahepatic biliary obstruction, liver
tumor, myocardial infarction, normal
bones of growing children, Paget's
disease, pregnancy, primary cirrhosis,
rheumatoid arthritis, and sarcoidosis.
Decreased levels with
hypophosphatemia, milk-alkali syndrome,
pernicious anemia, and scurvy.
Aspartate
amino-
transferase
Normal range:
Males: 820 U/l
Females: 540 U/l
Pregnancy, beriberi, uremia
or diabetic ketoacidosis can
falsely decrease aspartate
aminotransferase.
Aspartate aminotransferase is
elevated with exercise,
antihypertensives, cholinergic agents,
coumarin-type anticoagulants,
digitalis preparations, erythromycin,
isoniazid, methyldopa, oral
contraceptives, opiates, salicylates,
hepatotoxic medications, and
verapamil.
Increased levels with acute hemolytic
anemia, acute pancreatitis, cardiac
catheterization and angioplasty, cardiac
operations, drug-induced injury, heat
stroke, hepatic cirrhosis, hepatitis, hepatic
tumor, hepatic surgery, infectious
mononucleosis with hepatitis, multiple
traumas, muscle trauma, myocardial
infarction, primary muscle diseases,
progressive muscular dystrophy, recent
convulsions, recent skeletal surgery,
and severe burns. Decreased levels with
acute renal disease, beriberi, chronic
renal dialysis, diabetic ketoacidosis,
and pregnancy.
9
7
L
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o
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a
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o
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y
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e
s
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i
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t
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n
s
Table 7. continued
Test Reference values Endogenous interfering
factors
Exogenous interfering factors Interpretation
Bilirubin Normal range:
Total: 0.31.0 mg/dl;
Indirect: 0.20.8 mg/dl;
Direct: 0.10.3 mg/dl;
Values greater than
12 mg/dl should be
carefully considered.
Blood hemolysis and lipemia
can cause spurious results.
Blood levels of bilirubin elevated
with allopurinol, anabolic steroids,
antibiotics, antimalarials, ascorbic
acid, azathioprine, chlorpropamide,
cholinergics, codeine, dextran,
diuretics, epinephrine, meperidine,
methotrexate, methyldopa, monoamine
oxidase inhibitors, morphine, nicotinic
acid, oral contraceptives,
phenothiazines, quinidine, rifampin,
salicylates, steroids, sulfonamides,
theophylline, and vitamin A. Blood
levels of bilirubin decreased with
barbiturates, caffeine, penicillin and
high doses of salicylates.
Blood levels of conjugated (direct)
bilirubin increased with cholestasis
from drugs, Dubin-Johnson syndrome,
extrahepatic duct obstruction, gallstones,
liver metastasis, and Rotor's syndrome.
Blood levels of unconjugated (indirect)
increased with cirrhosis, Crigler-Najjar
syndrome, erythroblastosis fetalis, Gilbert
syndrome, hemolytic anemia, hemolytic
jaundice, hepatitis, large-volume blood
transfusions, pernicious anemia, sickle
cell anemia, transfusion reaction,
and sepsis.
g-Glutamyl
transpeptidase
Normal range: Male
and female (>45 years):
838 U/l; Female
(<45 years): 527 U/l
In late pregnancy values
can be depressed.
g-glutamyl transpeptidase increased
with alcohol, phenytoin, and
phenobarbital. g-glutamyl
transpeptidase decreased with
clofibrate and oral contraceptives.
Increased levels with alcohol,
Epstein-Barr virus, liver diseases,
myocardial infarction,
and pancreatic diseases.
Leucine
amino-
peptidase
Normal range:
Male: 80200 U/ml;
Female: 75185 U/ml
Pregnancy may be responsible
for a false elevation of
levels depending on the test
(e.g. enzyme method).
Leucine aminopeptidase will increase
with estrogens and progestins.
Increased with hepatobiliary disease.
5'-Nucleotidase Normal range: 0.01.6 U Increased levels with bile duct
obstruction, cholestasis, cirrhosis, hepatic
ischemia, hepatic necrosis, hepatic tumor,
hepatitis, and hepatotoxic drugs.
9
8
M
a
r
i
o
t
t
i
diseases can be identied and the severity of the
disease can be determined by examining levels of
this enzyme.
Alkaline phosphatase. The highest concentrations
of alkaline phosphatase are found in the liver, biliary
epithelium and bone. Alkaline phosphatase is used to
detect and monitor liver and bone diseases.
Aspartate aminotransferase. This enzyme is found
in high concentrations in metabolically active tissues
such as the liver. In acute hepatotoxic situations (e.g.
acute hepatitis, acute extrahepatic obstructions
including gallstones, etc.), levels of this enzyme will
rise 1020-fold. The ratio between aspartate amino-
transferase and alanine aminotransferase can also be
helpful in distinguishing different liver diseases.
When the ratio is greater than 1, alcoholic cirrhosis,
liver congestion and liver tumors may be present;
whereas a ratio less than 1 may indicate acute hepa-
titis, viral hepatitis or infectious mononucleosis.
Bilirubin. The heme fromhemoglobin is catabolized
to biliverdin, which is converted to an unconjugated
(indirect) bilirubin. In the liver, the indirect bilirubin
is attached to a glucuronide molecule resulting in a
conjugated (direct) bilirubin. In general, jaundice
caused by hepatotoxicity results in increases in in-
direct bilirubin, whereas jaundice resulting from
extrahepatic dysfunction exhibits elevated levels of
direct bilirubin. The total bilirubin levels are the sum
of the indirect and direct bilirubin quantities.
g-Glutamyl transpeptidase. The highest concentra-
tion of this enzyme is found in the liver and biliary
tract. It is a sensitive gauge of hepatobiliary disease
or excessive or chronic alcohol use.
Leucine aminopeptidase. The greatest concentra-
tion of this enzyme is found in the hepatobiliary
system. It is useful for diagnosing liver disorders.
5'-Nucleotidase. This is an enzyme that is specic to
the liver and is used to support the diagnosis of
hepatobiliary obstructive disease.
Immunologic studies
Acquired Immunodeficiency Syndrome (AIDS)
AIDS is characterized by the gradual destruction of
cell-mediated immunity (T cell) (15, 19). The human
immunodeciency virus causes direct destruction of
CD4

cells, such as T4 (helper) lymphocytes, macro-

phages and neuroglial cells. The resultant immuno-
deciency leads to opportunistic infections and
neoplasms that can be life threatening.
Laboratory tests (2) (see Table 8)
AIDS serology. This test is used to screen for and
diagnose HIV infection.
Lymphocyte immunophenotyping. Detection of prog-
ressive depletion of CD4 T lymphocytes can indicate if
the person is at risk for opportunistic infections.
Renal studies
The kidneys are vital organs that regulate uidvolume,
electrolyte balance and acid-base balance of body
uids, detoxify agents in the blood, regulate blood
pressure, eliminate wastes and aid in erythropoiesis (9).
Diagnostic tests (14) (see Table 9)
Creatinine. Creatinine is the catabolic product of
creatinine phosphate which is used for skeletal mus-
cle contraction. Creatinine is excreted entirely by the
kidneys and the amount in the blood is directly pro-
portional to renal excretory function and used to
diagnosis impaired renal function.
Creatinine clearance. Since creatinine is excreted
entirely by the kidneys, it is directly proportional to
the glomerular ltration rate.
Blood urea nitrogen (BUN). Urea is formed in the
liver as an end product of protein metabolism and
secreted in the blood where it is removed by the
kidneys. Blood urea nitrogen is related to the meta-
bolic function of the liver and excretory function of
the kidneys. It is therefore an indirect measure of
renal function and glomerular ltration rate as long
as there is normal liver function.
Laboratory studies of genetic diseases
that modify periodontitis
There are several genetic disorders (see Table 10)
that have been reported to have signicant effects
on the periodontium (12). With the exception of
Down's syndrome, these diseases have a number of
characteristics which make it highly unlikely that a
clinician will treat these individuals. The distinctive
attributes that make these diseases exceptional
99
Laboratory testing of systemic conditions
include an extremely low prevalence in the popula-
tion, the diagnosis of these diseases at or within the
rst few years following birth and lethality of many of
the diseases, particularly in the rst decade of life. All
of these traits make it unlikely that you will order a
test to diagnose or even manage these patients unless
you are associated with a large health science com-
plex. To put these diseases into prospective, a period-
ontist has a greater chance of being struck by
lightening (1:600,000), being killed by a falling air-
craft (1:320,000) or dying from an earthquake
(1:140,000), than one would have of treating a patient
with leukocyte adhesion deciency syndrome (1 per-
son in 1 million affected) or Papillon-Lefevre syn-
drome (1 person in 1 million affected).
Perspective of a clinician when
interpreting laboratory tests
As previously discussed, sensitivity is the ability of a
test to nd those with the disease and specicity
indicates the ability of a test to identify those without
the condition. Unfortunately, sensitivity and speci-
city are not much value to the practitioner because
they are measures of past test performance. For the
clinician, it is more important to interpret the test
results for those who are being tested. Therefore the
predictive value of the test needs to be known. The
positive predictive value of a test is the probability of
a patient with a positive test actually having a dis-
ease, while the negative predictive value is the prob-
ability of a patient with a negative test not having the
disease. Since the sensitivity and specicity of a test
are constant within the populations undergoing the
test, the predictive value of a test result depends not
only on the sensitivity of the test but also on the
prevalence of the condition within the population
being tested. For example, if the prevalence of a dis-
ease in Pittsburgh is 5%, the positive predictive value
of a test (with a 96% sensitivity) is 56%. However, if
the prevalence of that same disease is 20% in Colum-
bus, the positive predictive value using the same test
(with 96% sensitivity) is 86%. Therefore, the outcome
of the test is affected by the prevalence of the disease.
In conclusion, the clinician must make decisions that
are dependent on the importance of the disease in
question. If it is important not to miss a diagnosis, a
test with high sensitivity should be chosen. However,
if there are serious consequences concerning a posi-
tive result, the clinician may chose to give greater
emphasis to the test with high specicity in order
to reduce the chances of obtaining a false-positive.
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100
Mariotti
Table 9. Renal diseases (17, 28, 30)
Test Reference values Endogenous interfering
factors
Exogenous interfering factors Interpretation
Creatinine Normal range: Male: 0.61.2 mg/dl;
Female: 0.51.1 mg/dl;
Values >4 mg/dl are indicative of
impaired renal function that may
be serious.
Creatinine is increased with
a high diet of meat,
aminoglycosides, cimetidine,
and nephrotoxic drugs.
Increased levels with acromegaly, acute
tubular necrosis, diabetic nephropathy,
gigantism, glomerulonephritis,
pyelonephritis, nephritis, reduced renal
blood flow, rhabdomyolysis, and urinary
tract obstruction. Decreased levels with
debilitation and decreased muscle mass
due to diseases such as muscular
dystrophy and myasthenia gravis.
Creatinine
Clearance
Normal Range: Adult (<40 years)
Male: 107139 ml/min;
Female: 87107 ml/min.
Values decrease by 6.5 ml/min
for each decade of life after the
age of 20.
Pregnancy increases
creatinine clearance.
Creatinine clearance is
increased with exercise,
a diet high in meat,
aminoglycosides, cimetidine,
and nephrotoxic drugs.
Increased levels with exercise, high
cardiac output syndromes,
and pregnancy. Decreased levels with
conditions causing decreased glomerular
filtration rates (e.g. congestive heart
failure) and impaired renal function
(e.g. glomerulonephritis).
Blood Urea
Nitrogen (BUN)
Normal range: Adult: 1020 mg/dl.
Values >100 mg/dl are indicative of
impaired renal function that may
be serious.
In late pregnancy
BUN may be increased.
Increased levels with acute tubular
disease, bladder outlet obstruction, burns,
congestive heart failure, dehydration,
excessive protein catabolism, GI bleeding,
glomerulonephritis, hypovolemia,
myocardial infarction, nephrotoxic drugs,
pyelonephritis, renal failure, shock, sepsis,
starvation, and ureteral obstruction.
Decreased levels with liver failure,
negative nitrogen balance, nephritic
syndrome, and pregnancy.
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Table 10. Genetic disorders (3, 29)
Disease Characteristics Manifestation Etiology Frequency
Chediak-Higashi
syndrome
Oculocutaneous albinism, frequent
bacterial infections, large lysosomal
granules in the granulocytes
At birth and first few months of
life. Prenatal diagnosis is possible.
60% of individuals die by the age
of 4.
Autosomal recessive inheritance Rare: 10 published cases from
15 countries in 4 continents.
Chronic
Granulomatous
Disease
Defect in microbicidal activity
leading to recurrent pyogenic
infections with catalase-positive
microorganisms.
During early infancy to young
adulthood. Mortality is highest
in young children.
X-linked and autosomal
recessive inheritance
Rare: 4:1,000,000
Down's
Syndrome
Mental retardation with
characteristic physical appearance
(e.g. flat face with mongoloid slant,
etc.)
At birth. Prenatal diagnosis is
possible. Life expectancy is
reduced (presence of cardiac
defect is often fatal early in life).
Trisomy of chromosome 21 1:650
Ehrlers-Danlos
Syndrome
A group of diseases with
connective-tissue alterations
leading to hyperelastic skin,
hypermobility of joints, tissue
fragility, eye changes and bleeding
diathesis.
At birth. Life expectancy is
reduced.
Autosomal dominant transmission
in types I, II, III & VIII; autosomal
dominant and recessive transmission
of types IV & VII; X-linked recessive
transmission of type V; autosomal
recessive transmission of type VI
Low: 1:150,000
Hypophosphatasia Deficient calcification of the bones,
absent calcification of the calvaria,
craniosynostosis, bowed long
bones, fractures, hypercalcemia,
nephrocalcinosis
At birth or within the first 3 years.
One form is not diagnosed until
puberty. Infantile form can be
lethal.
Autosomal recessive inheritance Rare: 120 patients diagnosed
by 1972.
Leukocyte
Adhesion
Deficiency
Syndrome
Recurrent bacterial and fungal
infections and depressed
inflammatory responses despite
striking neutrophilia.
During infancy. Individuals with
severe deficiency can die during
infancy; moderate deficiency
individuals can live a normal
lifespan
Autosomal recessive inheritance Rare: 1:1,000,000
Papillon-Lefevre
Syndrome
Plantopalmar hyperkeratoses and
edentulism
At birth but not usually diagnosed
until eruption of primary teeth.
Normal lifespan.
Autosomal recessive inheritance Rare: estimated to be
1:1,000,000
1
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Table 11. Critical values for laboratory tests (30)
Test Low value Common causes and effects High value Common causes and effects
Calcium, serum <7 mg/dl Vitamin D or PTH deficiency:
tetany, seizures
>12 mg/dl Hyperparathyroidism: coma
Creatinine, serum >4 mg/dl Renal failure: coma
Glucose, blood <40 mg/dl Excess insulin administration:
brain damage
>300 mg/dl (with ketonemia
and electrolyte imbalance)
Diabetes: diabetic coma
Hemoglobin <8 g/dl Hemorrhage, vitamin B
12
or iron
deficiency: heart failure
>18 g/dl Chronic obstructive pulmonary disease:
thrombosis, polycythemia vera
Partial thromboplastin time >40 s, >70 s (for patient on
heparin)
Anticoagulation factor deficiency:
hemorrhage
pH, blood <7.2 Complex pattern of metabolic and
respiratory factors
>7.6 Complex pattern of metabolic and
respiratory factors
Platelet count <50,000/ml Bone marrow suppression: hemorrhage >500,000/ml Leukemia, reaction to acute bleeding:
hemorrhage
Potassium, serum <3 mEq/l Vomiting and diarrhea, diuretic therapy:
cardiotoxicity, arrhythmia, cardiac arrest
>6 mEq/l Renal disease diuretic therapy:
cardiotoxicity, arrhythmia
Prothrombin time >14 s, >20 s (for patient on
warfarin)
Anticoagulant therapy, anticoagulation
factor deficiency: hemorrhage
Sodium, serum <120 mEq/L Diuretic therapy: cardiac failure >160 mEq/l Dehydration: vascular collapse
White blood cell count <2000/ml Bone marrow suppression: infection >20,000/ml Leukemia: infection
White blood cell count, CSF >10/ml Meningitis, encephalitis: infection
1
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Table 12. Normal reference values for laboratory tests (17, 30)
Test Normal range
Hematology
Activated partial thromboplastin time 2536 s
Bleeding Time Modified template: 210 min
Template: 28 min
Ivy: 19 min
Duke: 13 min
Clot retraction 50%
Erythrocyte sedimentation rate Males: 010 mm/h
Females: 020 mm/h
Fibrin split products Screening assay: <10 mg/ml
Quantitative assay: <3 mg/ml
Fibrinogen, plasma 195365 mg/dl
Hematocrit Males: 4252%
Females: 3747%
Neonates: 5568%
Hemoglobin, total Males: 1418 g/dl
Males after middle age: 12.414.9 g/dl
Females: 1216 g/dl
Females after middle age: 11.713.8 g/dl
Partial thromboplastin time 6070 s
Platelet aggregation 35 min
Platelet count 150,000400,000/ml
Platelet survival 50% tagged platelets disappear within 84116 h: 100% disappear within 810 days
Prothrombin consumption time 20 s
Prothrombin time 1012.4 s
Red blood cell count Males: 4.76.1 million/ml venous blood
Females: 4.25.4 million/ml venous blood
Red cell indices Mean corpuscular volume: 8499 fl
Mean corpuscular hemoglobin: 2632 fl
Mean corpuscular hemoglobin concentration: 3036 g/dl
Reticulocyte count 0.52% of total red blood cell count
Thrombin time, plasma 1015 s
Blood chemistry
Acid phosphatase 0.51.9 U/l
Alanine aminotransferase Males: 1035 U/l
Females: 924 U/l
Alkaline phosphatase Males 19 years: 98251 U/l
Females 2465 years: 81282 U/l
Females 65 years: 119309 U/l
Amylase 18 years: 35115 U/l
Arterial blood gases pH: 7.357.45
PaO
2
: 75100 mm Hg
PaCO
2
: 3545 mm Hg
O
2
Cr: 1523%
SaO
2
: 94100%
HCO
3
-: 2226 mEq/l
104
Mariotti
Table 12. continued
Test Normal range
Aspartate aminotransferase Males: 820 U/l
Females: 540 U/l
Bilirubin Adults: direct, 0.10.3 mg/dl; indirect, 0.20.8 mg/dl
Neonates: total, 112 mg/dl
Blood urea nitrogen 820 mg/dl
Calcium, serum (atomic absorption) Males 22 years: 8.910.1 mg/dl
Females 19 years: 8.910.1 mg/dl
Carbon dioxide, total, blood 2234 mEq/l
Cholesterol, total 0240 mg/dl
C-reactive protein Negative
Creatine Males: 0.20.6 mg/dl
Females: 0.61 mg/dl
Creatine kinase, isoenzymes CK-BB: none
CK-MB: 07 U/l
CK-MM: 570 U/l
Creatine kinase, total Males 18 years: 52336 U/l
Females 18 years: 38176 U/l
Creatine Males: 0.81.2mg/dl
Females: 0.60.9 mg/dl
Ferritin Males: 12300 ng/ml
Females: 1050 ng/ml
Folic acid 525 ng/ml
Free thyroxine 0.83.3 ng/dl
Free triiodothyronine 0.20.6 ng/dl
g-glutamyltransferase Males: 838 U/l
Females <age 45: 527 U/l
Woman age 45: 838 U/l
Glucose, plasma, fasting 70100 mg/dl
Glucose, plasma, oral tolerance Peak at 160180 mg/dl, 3060 min after challenge dose
Glucose, plasma, 2 hour postprandial <165 mg/dl
Hydroxybutyric dehydrogenase (HBD) Serum HBD: 114290 U/ml
LD/HBD ratio: 1.21.6.1
Iron Males: 80180 mg/dl
Females: 60160 mg/dl
Lactate dehydrogenase (LD) Total: 48115 IU/l
LD
1
: 1426%
LD
2
: 2939%
LD
3
: 2026%
LD
4
: 816%
LD
5
: 616%
Lactic acid, blood 0.931.65 mEq/l
Leucine aminopeptidase Males: 80200 U/ml
Female: 75185 U/ml
Lipase <300 U/l
Lipoproteins HDL cholesterol: 2977 mg/dl
LDL cholesterol: 62185 mg/dl
105
Laboratory testing of systemic conditions
Table 12. continued
Test Normal range
Magnesium 1.52.5 mEq/l
Atomic absorption: 1.72.1.mg/dl
5'-Nucleotidase 0.01.6 U
Phosphates 1.82.6 mEq/l
Atomic absorption: 2.54.5 mg/dl
Potassium 3.85.5 mEq/l
Protein Total: 6.67.9 g/dl
Albumin fraction: 3.34.5 g/dl
a
1-
globulin: 0.10.4 g/dl
a
2-
globulin: 0.51 g/dl
b globulin: 0.71.2 g/dl
g globulin: 0.51.6g/dl
Sodium 135145 mEq/l
Thyroxine, total 513.5 mg/dl
Triglycerides Males: 40160 mg/dl
Females: 35135 mg/dl
Uric acid Males: 4.38.0 mg/dl
Females: 2.36.0 mg/dl
Vitamin B
12
160950 pg/ml
White blood cell differential, blood Neutrophils: 47.676.8%
Lymphocytes: 16.243%
Monocytes: 0.69.6%
Eosinophils:0.37.0%
Basophils: 0.32.0%
Urine chemistry
Amylase 1080 amylase U/h
Bence Jones protein Negative
Bilirubin Negative
Calcium Males: <275 mg/24 h
Females: <250 mg/24 h
Creatinine Males: 040 mg/24 h
Females: 080 mg/24 h
Creatinine clearance Males: 107139 ml/min
Females: 87107 ml/min
Glucose, urine Negative
17-Hydroxycorticosteriods Males: 4.512 mg/24 h
Females: 2.510 mg/24 h
17- Ketogenic steroids Males: 414 mg/24 h
Females: 212 mg/24 h
Ketones Negative
17-Ketosteroids Males: 621 mg/24 h
Females: 417mg/24 h
Protein 150 mg/24 h
Red blood cells 03 per high-power field
Sodium 30280 mEq/24 h
106
Mariotti
Whichever test is chosen for patient evaluation (see
Tables 11 and 12), take the time to become familiar
with and remain current with all aspects of the
laboratory test.
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Table 12. continued
Test Normal range
Sodium chloride 520 g/24 h
Urea Maximal clearance: 6499 ml/min
Uric acid 250750 mg/24 h
Urinalysis, routine Color: straw
Appearance: clear
Specific gravity: 1.0051.035
pH: 4.58
Epithelial cells: few
Casts: occasional hyaline casts
Crystals: present
Urine osmolality 24-hour urine: 300900 mOsm/kg
Random urine: 501,400 mOsm/kg
Urobilinogen Males: 0.32.1 Ehrlich units/2 h
Females; 0.11.1 Ehrlich units/2 h
Vanillylmandelic acid 0.76.8 mg/24 h
White blood cell count 04 per high-power field
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108
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