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142 Laboratory Medicine in Psychiatry and Behavioral Science
Heavy metal screening
Type of test Blood, 24-hour urine
Background and explanation
of test
Potentially toxic metals are found naturally in the environ-
ment and are used in various industrial processes. Toxic hu-
man exposure may occur due to accident, intentional
overdose, or the cumulative effects of chronic, low-level ex
-
posure. In the latter case, exposure is usually occupational or
occurs within the context of certain hobbies. Heavy metals
can contaminate air, water, soil, or food. One well-known ex
-
ample of exposure from food is mercury poisoning from fish
caught in polluted waters.
The term heavy metal refers to a range of metals, from alumi-
num to lead, with relatively high atomic weights. Different
laboratories offer different combinations of tests as heavy
metal screening panels. One commonly offered panel is a
blood screen for lead, mercury, and arsenic. Other metals
tested include aluminum, beryllium, bismuth, cadmium,
chromium, cobalt, copper, iron, manganese, molybdenum,
nickel, platinum, selenium, silicon, silver, thallium, and zinc.
Those metals with psychiatric or neurological toxic se
-
quelae—lead, manganese, and mercury—are discussed in the
Diseases and Cond itions chapter.
It should be noted that a panel of tests is not required for
screening; any one metal can be ordered separately. Heavy
metal testing is usually done on blood or a 24-hour urine sam
-
ple, although for some indications, other samples such as hair
or nails are used. Special containers are used to collect sam
-
ples to minimize extraneous metal contamination.
Interpretation of heavy metal screening results for acute toxic
exposures is complicated by the fact that these metals are in
the circulation for only a short time and are not present in
urine for an extended period. In addition, apparently healthy
people may have low levels of heavy metals present in blood
and urine that reflect environmental levels.
Relevance to psychiatry and
behavioral science
Heavy metals associated with neuropsychiatric signs and
symptoms include lead, manganese, and mercury. Lead poi-
soning is well known to produce behavioral and cognitive
problems in children and is associated with delirium, demen-
tia, motor deficits, mood and personality changes, fatigue,
weakness, and constitutional signs in patients of all ages.
Manganese poisoning is associated with parkinsonism cou-
pled with mood changes, psychosis, behavioral changes,
dementia, sleep disturbances, sexual dysfunction, headaches,
and speech problems.
Mercury poisoning can produce vague symptoms such as
fatigue, apathy, emotional instability, memory problems,
headache, ataxia, and paresthesias or can be associated with
specific deficits, including deafness, dysarthria, dysphagia,
and visual disturbances.
Preparation of patient None needed
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143 Laboratory Tests
Heavy metal screening (continued)
Indications • Confirming suspected toxic metal exposure
• Evaluating a patient with signs and symptoms of toxic
exposure
• Monitoring metal levels in a patient with known occu-
pational exposure
Reference range
See Lead Poisoning, Manganese Poisoning, and Mercury
Poisoning entries in the Diseases and Conditions chapter.
Critical value(s)
Increased levels
Decreased levels
Interfering factors
Cross-references Lead Poisoning
Manganese Poisoning
Mercury Poisoning
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed May 2010.
Brown JS: Environmental and Chemical Toxins and Psychiatric Illness. Washington, DC, American Psy-
chiatric Publishing, 2002
Hales RE, Yudofsky SC, Gabbard GO (eds): The American Psychiatric Publishing Textbook of Psychiatry.
Washington, DC, American Psychiatric Publishing, 2008
Kim JJ, Kim YS, Kumar V: Heavy metal toxicity: an update of chelating therapeutic strategies.J Trace
Elem Med Biol 54:226–231, 2019
Sadock BJ, Sadock VA, Ruiz P (eds): Kaplan and Sadock’s Comprehensive Textbook of Psychiatry. Phila-
delphia, PA, Lippincott Williams and Wilkins, 2009
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144 Laboratory Medicine in Psychiatry and Behavioral Science
Hematocrit
Type of test Blood
Background and explanation
of test
Hematocrit is a measure of the oxygen-carrying capacity of
the blood and the primary determinant of blood viscosity.
When the hematocrit is too low, oxygenation of tissues is com
-
promised; when hematocrit is too high, thrombotic risk in-
creases.
For this test, RBCs are separated from plasma by centrifuga-
tion, and the resulting RBC mass is measured. Alternatively,
the hematocrit can be calculated from the measured hemoglo
-
bin and MCV. As a rule, the hematocrit value is 3 times the
hemoglobin value.
Relevance to psychiatry and
behavioral science
A low hematocrit is associated with symptoms of fatigue,
weakness, somnolence, anhedonia, and depression. Patients
with restless legs syndrome may have a low hematocrit, and
symptoms of this condition may improve with interventions
to raise the hematocrit. Heavy smoking and lung disease
often cause secondary elevation of the hematocrit, and modi
-
fication of these health risks may lower it. High hematocrit in
the third trimester of pregnancy has been suggested as a bio
-
marker for postpartum depression and anxiety symptoms.
Preparation of patient None needed
Indications • Component of routine blood count
• Determining anemia (low hematocrit) or polycythemia
(high hematocrit)
Reference range Normal hematocrit is ~45%, with the following normal
ranges:
• Adult females: 36%–48%
• Adult males: 42%–52%
Critical value(s) Hematocrit < 20% associated with cardiac failure and death
Hematocrit >60% associated with spontaneous blood clot-
ting
Persistent elevation above the upper limit of normal for
>2 months should prompt referral to a hematologist for
evaluation. The risk of events such as large-vessel occlusion
increases with a hematocrit >45%.
Increased levels • Erythrocytosis
• Polycythemia vera
• Shock, with hemoconcentration
• Heavy smoking and lung disease
• High altitude
Decreased levels • Anemia
• Leukemia, lymphoma, Hodgkin’s disease, myeloprolif-
erative disorders
• Adrenal insufficiency
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145 Laboratory Tests
Hematocrit (continued)
Decreased levels (continued) • Chronic disease
• Acute and chronic blood loss
• Hemolytic reaction (from incompatible blood transfu-
sion, drug reactions, or reactions to chemicals, infec-
tions, or physical agents)
• Old age, female sex, pregnancy
Interfering factors Age affects the hematocrit, with differing normal ranges
from birth to adulthood. Patients older than 60 years tend to
have lower hematocrits.
Females generally have lower hematocrit values than males.
Pregnancy is associated with decreased hematocrit values.
At high altitudes, hematocrit values are increased.
Values tend to be unreliable immediately after acute blood
loss or transfusion.
Cross-references Anemia
Complete Blood Count
Restless Legs Syndrome
Brun JF, Varlet-Marie E, Richou M, et al: Seeking the optimal hematocrit: may hemorheological modelling
provide a solution?Clin Hemorheol Microcirc 69(4):493–501, 2018
Chernecky CC, Berger BJ: Laboratory Tests and Diagnostic Procedures, 5th Edition. St. Louis, MO,
WB Saunders, 2008
Fischbach FT, Fischbach MA: A Manual of Laboratory and Diagnostic Tests, 10th Edition. Philadelphia,
PA, Wolters Kluwer Health/Lippincott Williams and Wilkins, 2018
Roomruangwong C, Kanchanatawan B, Sirivichayakul S, Maes M: Antenatal depression and hematocrit
levels as predictors of postpartum depression and anxiety symptoms.Psychiatry Res 238:211–217,
2016
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146 Laboratory Medicine in Psychiatry and Behavioral Science
Hemoglobin
Type of test Blood
Background and explanation
of test
Hemoglobin binds and carries oxygen and carbon dioxide in
RBCs. The oxygen-carrying capacity of the blood is thus di
-
rectly related to the hemoglobin concentration. Hemoglobin
also serves as a buffer for extracellular fluid to maintain phys
-
iological pH. The hemoglobin value is generally one-third
that of the hematocrit.
Several heritable hemoglobin variants exist, affecting almost
7% of the world population. Hemoglobin S, C, and E are the
most common. Hemoglobin S is associated with sickle cell
disease. Hemoglobin C and E are known to cause anemia.
Relevance to psychiatry and
behavioral science
See Hematocrit.
Preparation of patient None needed
Indications •
Component of routine CBC
• Screening for anemia
• Determining severity of anemia
• Monitoring response to treatment for anemia
• Evaluating polycythemia
Reference range Adult females: 12.1–15.1 g/dL
Adult males: 13.8–17.2 g/dL
Critical value(s) <5.0 g/dL associated with heart failure and death
>20.0 g/dL associated with capillary clogging
Increased levels • Polycythemia vera
• Congestive heart failure
• Chronic obstructive pulmonary disease
Decreased levels •
Iron deficiency anemia
• Thalassemia
• Pernicious anemia
• Hemoglobinopathies
• Liver disease
• Hypothyroidism
• Hemorrhage
• Hemolytic anemia (e.g., due to drug reactions, transfusion
of incompatible blood, infectious disease, chemical expo-
sure, burns, or artificial heart valves)
• Systemic diseases (e.g., Hodgkin’s disease, leukemia,
lymphoma, lupus, sarcoidosis, carcinomatosis)
Interfering factors Increased hemoglobin seen with extreme exercise and in
those living at high altitude.
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147 Laboratory Tests
Hemoglobin (continued)
Interfering factors (continued) Decreased hemoglobin seen in pregnancy and with excessive
fluid intake.
Hemoglobin variants may confound hemoglobin measure-
ment.
Cross-references Anemia
Complete Blood Count
Chernecky CC, Berger BJ: Laboratory Tests and Diagnostic Procedures, 5th Edition. St. Louis, MO,
WB Saunders, 2008
Fischbach FT, Fischbach MA: A Manual of Laboratory and Diagnostic Tests, 10th Edition. Philadelphia,
PA, Wolters Kluwer Health/Lippincott Williams and Wilkins, 2018
Hasan MN, Fraiwan A, An R, et al: Paper-based microchip electrophoresis for point-of-care hemoglobin
testing.Analyst 145(7):2525–2542, 2020
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148 Laboratory Medicine in Psychiatry and Behavioral Science
Hemoglobin A1C (HbA1C)
Type of test Blood
Background and explanation
of test
HbA1C is a form of glycosylated hemoglobin—glucose
bound to hemoglobin—produced slowly over the 120-day life
span of the RBC, with the amount formed proportional to the
amount of glucose present in the blood. The measured
HbA1C value reflects the average blood sugar level in
the
2–3 months before the test, thus providing a longer-term view
of blood sugar control for patients with diabetes.
HbA1C is reported as a percentage of total hemoglobin. This
test does not replace fasting blood sugar checks by blood
draw or home glucose monitoring, which are required to de
-
termine whether dietary changes or immediate intervention
is needed.
To facilitate comparison of these numbers, the American
Diabetes Association recommends that HbA1C values be
converted to estimated average glucose (eAG) values, which
correspond more closely to glucose meter results. The con
-
version can be made using published tables or the following
formula: 28.7×HbA1C–46.7=eAG.
Relevance to psychiatry and
behavioral science
For patients with diabetes, this test can be ordered routinely
with admission lab tests. It is useful in the detection of poor
compliance with diabetic regimens. Patients with symptoms
of the metabolic syndrome should be considered for HbA1C
testing.
Preparation of patient No fasting necessary
Indications •
Baseline HbA1C testing for adults ≥ 45 years. If normal,
repeat every 3 years.
• Baseline HbA1C testing for patients <45 years who are
overweight and have risk factors for diabetes.
• Routine health maintenance for patients with diabetes
(type 1 or type 2): every 6 months for those meeting treat-
ment goals, with stable glycemic control; every 3 months
for those whose treatment has been changed or who are
not meeting treatment goals.
Reference range Normal: <5.7%
Prediabetes: 5.7%–6.4%
Diabetes: ≥6.5%
Critical value(s) <4% is associated with increased all-cause mortality
≥8% indicates increased
risk
of diabetic complications
>15% signifies uncontrolled diabetes
14.3%–20% corresponds to ketoacidosis
Increased levels •
Diabetes
• Prediabetes
Decreased levels Associated with increased all-cause mortality
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149 Laboratory Tests
Hemoglobin A1C (HbA1C) (continued)
Interfering factors Numerous conditions are associated with falsely increased
HbA1C levels, including anemia with reduced RBC turnover,
uremia, asplenia, severe hypertriglyceridemia, severe hyper
-
bilirubinemia, chronic alcohol ingestion, chronic salicylate
ingestion, and chronic opioid ingestion.
Conditions associated with falsely decreased HbA1C levels
include anemia from blood loss, pregnancy, splenomegaly,
vitamin E ingestion, monoclonal antibodies, and the drugs
ribavirin and interferon-α.
Falsely increased or decreased HbA1C levels can result from
RBC transfusions, hemoglobin variants, and vitamin C inges
-
tion.
Cross-references Diabetes Mellitus
Glucose
Hyperglycemia
Metabolic Syndrome
Carson AP, Fox CS, McGuire DK, et al: Low hemoglobin A1c and risk of all-cause mortality among US
adults without diabetes.Circ Cardiovasc Qual Outcomes 3(6):661–667, 2010
Guo W, Zhou Q, Jia Y, Xu J: Increased levels of glycated hemoglobin A1c and iron deficiency anemia: a
review. Med Sci Monit 25:8371–8378, 2019
Hasan MN, Fraiwan A, An R, et al: Paper-based microchip electrophoresis for point-of-care hemoglobin
testing.Analyst 145(7):2525–2542, 2020
Nathan DM, Griffin A, Perez FM, et al: Accuracy of a point-of-care hemoglobin A1c assay. J Diabetes Sci
Technol 13(6):1149–1153, 2019
Radin MS: Pitfalls in hemoglobin A1c measurement: when results may be misleading.J Gen Intern Med
29(2):388–394, 2014
Wright LA, Hirsch IB: Metrics beyond hemoglobin A1C in diabetes management: time in range, hypogly-
cemia, and other parameters. Diabetes Technol Ther 19(S2):S16–S26, 2017
https://t.me/med1917
150 Laboratory Medicine in Psychiatry and Behavioral Science
Hepatitis panel
Type of test Blood
Background and explanation
of test
When a patient with no prior history of hepatitis presents
with signs and symptoms suggestive of acute infectious
hepatitis, a screening panel is ordered. In the United States,
screening is carried out for hepatitis A, B, and C infection
simultaneously, except in the case of a known exposure to a
specific type. The panel includes the following tests:
• Hepatitis A virus antibody, IgM
• Hepatitis B virus core antibody, IgM
• Hepatitis B virus surface antigen with reflex to confirma-
tion
• Hepatitis C virus antibody
If the patient presents with signs and symptoms suggestive
of acute hepatitis and has a known history of hepatitis B in
-
fection, the patient is tested for co-infection with delta hep-
atitis (hepatitis D). If the patient presents with signs and
symptoms like those of hepatitis A but is seronegative, test
-
ing for hepatitis E by hepatitis E IgM antibody may be indi-
cated.
Relevance to psychiatry and
behavioral science
Hepatitis is highly prevalent among patients in psychiatric
care. Hepatitis A and E are usually mild, self-limited dis
-
eases with complete recovery, whereas hepatitis B, C, and D
can cause acute liver failure. Hepatitis B and C often result
in chronic infection leading to cirrhosis or hepatocellular
carcinoma.
Hepatitis C infection is often associated with neuropsychiat-
ric disorders, including cognitive impairment, stroke, and
peripheral neuropathy. Hepatitis E infection is associated
with Guillain-Barré syndrome, meningoencephalitis, and
brachial plexus neuritis.
Hepatitis A and E are transmitted by the fecal-oral route,
involving contaminated food or water. Hepatitis B, C, and D
are transmitted through body fluid exposure, most com
-
monly from sexual contact or needle sharing.
Preparation of patient None needed
Indications •
New-onset jaundice, dark urine, nausea, and/or an-
orexia
• Exposure to hepatitis
• Elevated liver enzymes
• Suspicion of chronic hepatitis
Reference range Negative testing for hepatitis A antibody, hepatitis B core
antibody and surface antigen, and hepatitis C antibody
Critical value(s) None
https://t.me/med1917
151 Laboratory Tests
Hepatitis panel (continued)
Positive test Hepatitis A antibody positive: acute hepatitis A
Hepatitis B antibody positive and surface antigen positive: acute
hepatitis B or chronic hepatitis (further testing indicated)
Hepatitis C antibody positive: acute hepatitis C or chronic hep-
atitis (further testing indicated)
Negative test Negative testing for hepatitis A antibody, hepatitis B core
antibody and surface antigen, and hepatitis C antibody
Interfering factors Individuals vaccinated for hepatitis B but never exposed
will show only surface antibody positivity.
False-negative results for hepatitis C may occur in hemodi-
alysis patients and those who are immunocompromised.
Hemolyzed or lipemic specimens, those containing particu-
late material, or heat-inactivated specimens invalidate re-
sults.
Cross-references Hepatitis, Viral
Almeida PH, Matielo CEL, Curvelo LA, et al: Update on the management and treatment of viral hepati-
tis. World J Gastroenterol 27(23):3249–3261, 2021
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed July 2021.
Bart G, Piccolo P, Zhang L, et al: Markers for hepatitis A, B and C in methadone-maintained patients: an
unexpectedly high co-infection with silent hepatitis B. Addiction 103:681–686, 2008
Castaneda D, Gonzalez AJ, Alomari M, et al: From hepatitis A to E: a critical review of viral hepati-
tis. World J Gastroenterol 27(16):1691–1715, 2021
Fontana RJ, Engle RE, Gottfried M, et al: Role of hepatitis E virus infection in North American patients
with severe acute liver injury. Clin Transl Gastroenterol 11(11):e00273, 2020
Jha AK, Kumar G, Dayal VM, et al: Neurological manifestations of hepatitis E virus infection: an over-
view. World J Gastroenterol 27(18):2090–2104, 2021
https://t.me/med1917
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