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Lupus Blood Tests

Blood Tests Used in the Diagnosis of Lupus

Antibodies form in the body as a response to infection. When an invader


(antigen) enters the body, white blood cells known as B lymphocytes react
by making special types of proteins called antibodies. Antibodies are your
bodys way of remembering an antigen; if it enters the body again, the
antibodies will recognize it, combine with it, and neutralize it to prevent you
from becoming infected. However, with autoimmune diseases such as lupus,
the immune system can produce antibodies (auto-antibodies) that attack
your bodys cells as though they were invaders, causing inflammation,
damage, and even destruction. Several blood tests can be performed to
detect specific auto-antibodies and help make the diagnosis of lupus. These
blood tests are not conclusive by themselves, but combining the tests with
certain physical findings can help to corroborate a diagnosis.

Anti-Nuclear Antibody (ANA) Test

Anti-nuclear antibodies (ANA) are autoantibodies to the nuclei of your cells.


98% of all people with systemic lupus have a positive ANA test, making it the
most sensitive diagnostic test for confirming diagnosis of the disease. The
test for anti-nuclear antibodies is called the immunofluorescent antinuclear
antibody test. In this test, a blood sample is drawn and sent to a laboratory.
Serum from the blood sample is then added to a microscopic slide prepared
with specific cells (usually sections of rodent liver/kidney or human tissue
culture cell lines) on the slide surface. If the patient has antinuclear
antibodies, their serum will bind to the cells on the slide. Then, a second
antibody tagged with a fluorescent dye is added so that it attaches to the
serum antibodies and cells that have bound together. Lastly, the slide is
viewed using a fluorescence microscope, and the intensity of staining and
pattern of binding are scored at various dilutions. The test is read as positive
if fluorescent cells are observed.
Usually, the results of the ANA test are reported in titers and patterns. The
titer gives information about how many times the lab technician diluted the
blood plasma to get a sample of ANAs. Each titer involves doubling the
amount of test fluid, so that the difference between a titer of 1:640 and
1:320 is one dilution. A titer above a certain level then qualifies as a positive
test result. ANA titers may increase and decrease over the course of the
disease; these fluctuations do not necessarily correlate with disease activity.
Thus, it is not useful to follow the ANA test in someone already diagnosed
with lupus.

The pattern of the ANA test can give information about the type of
autoimmune disease present and the appropriate treatment program. A
homogenous (diffuse) pattern appears as total nuclear fluorescence and is
common in people with systemic lupus. A peripheral pattern indicates that
fluorescence occurs at the edges of the nucleus in a shaggy appearance; this
pattern is almost exclusive to systemic lupus. A speckled pattern is also
found in lupus. Another pattern, known as a nucleolar pattern, is common in
people with scleroderma.

It is important to realize that even though 98% of people with lupus will have
a positive ANA, ANAs are also present in healthy individuals (5-10%) and
people with other connective tissue diseases, such as scleroderma and
rheumatoid arthritis. Moreover, about 20% of healthy women will have a
weakly positive ANA, and the majority of these people will never develop any
signs of lupus. One source cites that some ten million Americans have a
positive ANA, but fewer than 1 million of them have lupus. Therefore, a
positive ANA test alone is never enough to diagnosis systemic lupus. Rather,
a physician will order an ANA test if the patient first exhibits other signs of
lupus. This is because by itself, the test has low diagnostic specificity for
systemic lupus, but its value increases as a patient meets other clinical
criteria. It is possible for people with lupus to have a negative ANA, but these
instances are rare. In fact, only 2% of people with lupus will have a negative
ANA. People with lupus who have a negative ANA test may have anti-Ro/SSA
or antiphospholipid antibodies.

Other Diagnostic Tests

In people with a positive ANA, more tests are usually performed to check for
other antibodies that can help to confirm the diagnosis. Certain
autoantibodies and substances in the blood can give information about which
autoimmune disease, if any, is present. To check for these antibodies,
doctors usually order what is called an ANA panel, which checks for the
following antibodies: anti-double-stranded DNA, anti-Smith, anti-U1RNP, anti-
Ro/SSA, and anti-La/SSB. Some laboratories also include other antibodies in
their panel, including antinucleoprotein, anticentromere, or antihistone.

Anti-dsDNA Antibody

The anti-double-stranded DNA antibody (anti-dsDNA) is a specific type of


ANA antibody found in about 30% of people with systemic lupus. Less than
1% of healthy individuals have this antibody, making it helpful in confirming
a diagnosis of systemic lupus. [The absence of anti-dsDNA, however, does
not exclude a diagnosis of lupus.] The presence of anti-dsDNA antibodies
often suggests more serious lupus, such as lupus nephritis (kidney lupus).
When the disease is active, especially in the kidneys, high amounts of anti-
DNA antibodies are usually present. However, the anti-dsDNA test cannot be
used to monitor lupus activity, because anti-dsDNA can be present without
any clinical activity. Three tests are currently used to detect anti-dsDNA
antibodies, namely enzyme-linked immunosorbent assay (ELISA), the
Crithidia luciliae immunofluorescence test, and a test called
radioimmunoassay.

Anti-Smith Antibody

An antibody to Sm, a ribonucleoprotein found in the nucleus of a cell, is


found almost exclusively in people with lupus. It is present in 20% of people
with the disease (although the incidence varies among different ethnic
groups), but it is rarely found in people with other rheumatic diseases and its
incidence in healthy individuals is less than 1%. Therefore, it can also be
helpful in confirming a diagnosis of systemic lupus. Unlike anti-dsDNA, anti-
Sm does not correlate with the presence of kidney lupus. Prospective studies
have been performed as to whether anti-Sm correlates with lupus flares and
disease activity, although evidence seems to suggests that it does not. The
anti-Sm antibody is usually measured by one of four methods: ELISA,
counterimmunoelectrophoreses (CIE), immunodiffusion, or hemagglutination.

Anti-U1RNP Antibody

Anti-U1RNP antibodies are commonly found along with anti-Sm antibodies in


people with SLE. The incidence of anti-U1RNP antibodies in people with lupus
is approximately 25%, while less than 1% of healthy individuals possess this
antibody. However, unlike anti-dsDNA and anti-Sm antibodies, anti-U1RNP
antibodies are not specific to lupus; they can be found in other rheumatic
conditions, including rheumatoid arthritis, systemic sclerosis, Sjogrens
syndrome, and polymyositis.
Anti-U1RNP has shown to be associated with features of scleroderma,
including Raynauds phenomenon; it has also been linked to other conditions,
such as Jaccouds arthropathy, a deformity of the hand caused by arthritis.
Levels of anti-U1RNP may fluctuate in individuals over time, but this
fluctuation has not proven to be a significant indicator of disease activity.

Anti-Ro/SSA and Anti-La/SSB Antibodies

Anti-Ro/SSA and Anti-La/SSB are antibodies found mostly in people with


systemic lupus (30-40%) and primary Sjogrens syndrome. They are also
commonly found in people with lupus who have tested negative for anti-
nuclear antibodies. Anti-Ro and anti-La can also be found in other rheumatic
diseases, such as systemic sclerosis, rheumatoid arthritis, and polymyositis,
and are present in low titers in about 15% of healthy individuals. These
antibodies are not highly specific for systemic lupus, but they are associated
with certain conditions, including extreme sun sensitivity, a clinical subset of
lupus called subacute cutaneous lupus erythematosus (SCLE), and a lupus-
like syndrome associated with a genetic deficiency of a substance called
complement (a system of proteins that helps mediate your bodys immune
response). In addition, babies of mothers with anti-Ro and anti-La antibodies
are at an increased risk of neonatal lupus, an uncommon condition that
produces a temporary rash and can lead to congenital heart block. Therefore,
women with lupus who wish to become pregnant should be tested for these
antibodies.

Anti-Histone Antibodies

Antibodies to histones, proteins that help to lend structure to DNA, are


usually found in people with drug-induced lupus (DIL), but they can also be
found in people with systemic lupus. However, they are not specific enough
to systemic lupus to be used to make a concrete diagnosis.

Serum (blood) Complement Test

A serum complement test measures the levels of proteins consumed during


the inflammatory process. Thus, low complement levels reflect that
inflammation is taking place within the body. Variations in complement levels
exist in different individuals simply due to genetic factors.

Antiphospholipid Antibodies

Antiphospholipid antibodies are antibodies directed against phosphorus-fat


components of your cell membranes called phospholipids, certain blood
proteins that bind with phospholipids, and the complexes formed when
proteins and phospholipids bind. Approximately 50% of people with lupus
possesses these antibodies, and over a twenty-year period of time, one half
of lupus patients with one of these antibodiesthe lupus anticoagulantwill
experience a blood clot. People without lupus can also have antiphospholipid
antibodies.

The most commonly discussed antiphospholipid antibodies are the lupus


anticoagulant (LA) and anticardiolipin antibody (aCL). These two antibodies
are often found together, but can also be detected alone in an individual.
Other antiphospholipid antibodies include anti-beta 2 glycoprotein 1 (anti-2
GPI), anti-prothrombin, and the false-positive test for syphilis. Like other
antibodies involved in lupus that are directed against self (auto-antibodies),
antiphospholipid antibodies can come and go or increase and decrease.

The presence of an antiphospholipid antibody such as the lupus


anticoagulant and anticardiolipin antibody in an individual is associated with
a predisposition for blood clots. Blood clots can form anywhere in the body
and can lead to stroke, gangrene, heart attack, and other serious
complications. In people with lupus, the risk of clotting does not necessarily
correlate with disease activity, so the presence of these antibodies can cause
problems even when a persons lupus is in control. Complications of
antiphospolipid antibodies in lupus include fetal loss and/or miscarriages,
blood clots of the veins or arteries (thromboses), low platelet counts
(autoimmune thrombocytopenia), strokes, transient ischemic attacks (stroke
warnings), Libman-Sacks endocarditis (formation of a clot on a specific heart
valve), pulmonary emboli, and pulmonary hypertension.

Many people with antiphospholipid antibodies have a purple or reddish lacy


pattern just under their skin known as livedo. This pattern is especially
apparent on the extremities (i.e., the arms and legs). It is important to
realize, however, that having livedo does not necessarily mean one has
antiphospholipid antibodies; rather, doctors acknowledge a correlation
between the two conditions. Livedo can be associated with other diseases of
the blood vessels, but in fact, many perfectly healthy women also experience
the condition.

Antiphospholipid Antibody Syndrome (APS)


Individuals who experience complications from antiphospholipid antibodies
are diagnosed with Antiphospholipid Antibody Syndrome (APS). This
condition can occur both in people with lupus and those without lupus. Fifty
percent of people with lupus have APS. The presence of one or more clinical
episodes of thromboses (blood clots) and/or complications during pregnancy,
such as miscarriage or premature birth, in conjunction with a significant level
of anticardiolipin antibodies, antiphospholipid antibodies, and/or anti-2 GPI
anti- antibodies usually indicates the presence of APS. When APS is the sole
diagnosis, and no other connective tissue diseases are present, APS is often
said to be the primary diagnosis; when APS is present in association with
lupus or another connective tissue disease, APS is said to be secondary.
This classification is controversial, however, because some people with
primary APS (about 8%) later develop lupus, suggesting a connection
between the two conditions.

Types of Antiphospholipid Antibodies


False-Positive Test for Syphilis
In the 1940s, when it was common for people to have premarital exams,
doctors realized that some women with lupus tested positive for syphilis.
Further studies indicated that 1 in 5 people with lupus had a false-positive
syphilis test. The syphilis test of those daysthe Wasserman testwas
dependant on an antibody found in syphilis patients called reagin. The
substance to which this antibody reacts is cardiolipin, so the individuals with
a false-positive syphilis test actually had a form of anticardiolipin antibodies.
The false-positive syphilis test was the first recognized test for
antiphospholipid antibodies, but it is now known that people can have
antiphospholipid antibodies without having a false-positive syphilis test and
vice versa. The false-positive test is not associated with an increased risk of
blood clots in all medical studies performed in the past, but certain studies,
including the Johns Hopkins Lupus Cohort, suggest that there is a connection.
The false-positive syphilis test was one of the first three recognized
indications of antiphospholipid antibodies. The other two were the lupus
anticoagulant and anticardiolipin antibody.

Lupus Anticoagulant
In the late 1940s, it was found that an antibody present in some lupus
patients prolonged a clotting test dependent on phospholipids. For this
reason, it was thought that this antibody increased the tendency to bleed,
and thus it was deemed the lupus anticoagulant. However, this name is now
recognized as a misnomer for two reasons. First, the term anticoagulant is
a false label, since lupus anticoagulant actually increases the ability of the
blood to clot. Second, the term lupus in the name of the antibody is
misleading, since more than half of all people who possess this antibody do
not have lupus.

Tests called coagulation tests are used to detect the lupus anticoagulant
(LA). Remember that even though the lupus anticoagulant causes the blood
to clot more easily in vivo (i.e., in a persons body), they actually cause
prolonged clotting times in vitro (i.e., in a test tube). Therefore, if it takes
more time than normal for the blood to clot, the lupus anticoagulant is
usually suspected. The activated partial thromboplastin time (aPTT) is often
used to test for LA. If this test is normal, more sensitive coagulation tests are
performed, including the modified Russell viper venom time (RVVT), platelet
neutralization procedure (PNP), and kaolin clotting time (KCT). Normally, two
of these tests (the apt and the RVVT) are performed to detect whether lupus
anticoagulant is present.

Anticardiolipin Antibody
Even though the false-positive syphilis test and the lupus anticoagulant were
identified in the 1940s, the link between these entities was not investigated
until the 1980s, when a researcher at the Graham Hughes laboratory in
Britain named Nigel Harris began looking at antibodies to the phospholipid
antigens. Harris realized that cardiolipin was a major element of the false-
positive syphilis test, and he developed a more specific test for the antibody.
He also determined that the presence of these anticardiolipin antibodies was
associated with recurrent thromboses (blood clots) and pregnancy losses.
Others in Hughes laboratory began to publish studies showing the link
between anticardiolipin antibodies and stroke, deep vein thrombosis (DVT),
recurrent pregnancy loss, livedo, seizures, and other conditions. In fact, what
we now know as antiphospholipid syndrome was known as the anticardiolipin
syndrome even though other antiphospholipids, namely the lupus
anticoagulant, were known to produce similar effects.

There are different classes (isotypes) of anticardiolipin antibody, namely IgG,


IgM, and IgA. IgG is the anticardiolipin antibody type most associated with
complications. An enzyme-linked immunosorbent assay (ELISA) is used to
test for anticardiolipin antibodies. One can test for all isotypes at once, or
they can be detected separately. High levels of the IgM isotype are
associated with autoimmune hemolytic anemia, a condition in which an
individuals immune system attacks their red blood cells.

Anti-beta2 glycoprotein 1
Beta2 glycoprotein 1 is the protein in the body to which anticardiolipin
antibodies bind, and it is also possible to measure antibodies to beta2
glycoprotein 1. An individual can be positive for anticardiolipin antibodies
and negative for anti-2 GPI and vice versa, and detection of anti-2 GPI is
not yet part of routine testing done for patients with an increased likelihood
of blood clots.

Screening Laboratory Tests

The following tests provide the starting point of any medical workup. By
comparing your test results to the normal values for your age, sex, and
personal circumstances (i.e., medications you may be taking, health
conditions you might have, etc.), your doctor can monitor changes in your
disease activity and overall health.

Complete Blood Count (CBC) A complete blood count (CBC) is the most
commonly performed lab test in the U.S. and is used to analyze red blood
cells (RBCs), white blood cells (WBCs), and platelets. Many people with
systemic lupus have abnormal CBCs.

Blood Chemistry Panel A blood chemistry panel is a common test used to


evaluate anywhere from 7-25 individual components of your blood. From
these tests, doctors can glean information on the function of many vital
organs and substances, including your kidneys, blood glucose, cholesterol,
liver, thyroid.

Urinalysis A complete urinalysis evaluates several different aspects of your


urine through physical, chemical, and microscopic examination. In lupus
treatment, a urinalysis is often used to monitor protein leakage (indicating
kidney involvement) and identify and assess urinary tract infections (UTIs).

Blood Chemistry Panel

A blood chemistry panel is another common test used to evaluate a variety


of components. Usually, it consists of about 7-25 tests. The information
below is meant to provide an overview of these tests. Your doctor will
counsel you regarding the results of your personal blood work and laboratory
tests.

Kidney Function Tests

The creatinine blood test and blood urea nitrogen (BUN) test are used to
assess kidney function in people with lupus kidney disease (nephritis).

Creatinine: Creatinine is produced by your muscles as they breakdown


creatine, a substance involved in muscle contraction. Creatinine is formed at
a constant rate in the body and excreted by the kidneys, so by evaluating the
amount of creatinine in your blood, your doctor can determine how efficiently
your kidneys are working. Creatinine levels are measured by taking a sample
of blood from your vein; then, the concentration of creatinine in your blood is
compared to a standard amount for your age and sex. Increased blood
creatinine levels may indicate an increase in lupus involvement of the kidney.
Other conditions, such as high blood pressure or diabetes, can also cause
elevated creatinine levels.

Sometimes individuals are asked to provide a 24-hour urine sample for


further assessment. The combination of blood and urine samples can be used
to evaluate a creatine clearancehow effectively your kidneys filter small
molecules, such as creatinine, from your blood. In addition, since creatinine is
usually removed from the blood at a constant rate, blood creatinine levels
can be used as a standard by which doctors can compare other urine or blood
tests. Your serum (blood) creatinine level can also be combined with your
age, weight, and gender to evaluate your estimated glomerular filtration rate
(eGFR). Glomeruli are tiny ball-shaped structures in your kidneys that help
filter blood and prevent the loss of valuable substances, such as blood cells
and proteins. The eGFR is an educated estimate of the amount of blood that
is filtered per minute by your glomeruli and is often used to detect kidney
damage.

Blood urea nitrogen (BUN): The BUN test measures the amount of urea
nitrogen in your blood. The liver produces nitrogen in the form of ammonia
(NH3) as it breaks down proteins into their constituent amino acids. From the
liver, urea travels in your blood to the kidneys, which filter the urea and flush
it from your body in the form of urine. To evaluate an individuals BUN level,
blood is drawn from the vein, and the concentration of urea nitrogen in the
blood is evaluated and compared to a standard value for that persons age
range. Even though increased protein levels in a persons diet can cause their
blood urea nitrogen levels to increase, elevated BUN may suggest kidney
involvement due to lupus or another condition such as dehydration that
causes decreased blood flow to the kidneys. Low BUN levels are uncommon
and are usually not as important; they can suggest certain conditions, such
as malnutrition, over-hydration, or liver disease, but doctors usually use other
tests to monitor these conditions.

Blood Glucose (Sugar) Test


Tests of blood glucose levels are performed to determine if an individuals
blood glucose is in normal range. This test helps to detect hyperglycemia
(high blood sugar), hypoglycemia (low blood sugar), and diabetes (which can
occur after long-term steroid therapy). Glucose is a simple sugar that your
body gets from the food you eat. The cells of your body need glucose to
obtain energy, and they cannot function without it. When we think of
providing our bodies with energy, we usually think about movement and
physical activity. However, glucose is also vital to the cells of your brain and
central nervous system.

The amount of glucose in your blood is controlled by a feedback mechanism


involving two hormones, insulin and glucagon. These hormones work to
ensure that your blood contains the right amount of glucose so that your
cellsincluding those in your brain and central nervous systemcan
function correctly. When your body takes in glucose after a meal, insulin is
secreted by cells in your pancreas (beta cells) in order to lower your blood
glucose to the appropriate level. When your blood sugar gets too low,
glucagon is secreted by alpha cells of the pancreas in order to raise glucose
levels. Disruptions in this feedback mechanism can be harmful to your body.
In people with diabetes, the body either does not make enough insulin or
does not use it properly. High or low blood sugar levels caused by diabetes or
other conditions can be serious if not kept in check.
Blood glucose levels are usually evaluated when the patient is fasting, but
they can also be taken at random, after a meal, or in a challenge test in
which a person consumes a certain amount of glucose to challenge their
system and track the way his/her body deals with glucose over time.
Diabetics usually monitor their own blood glucose levels at home.

Fasting Lipid Profile

A lipid profile is a group of tests that includes measurements of total


cholesterol, HDL-cholesterol (good cholesterol), LDL-cholesterol (bad
cholesterol), and triglycerides (fats), all of which are risk factors for
cardiovascular disease. It is important that your doctors perform fasting lipid
profiles if your cholesterol has been elevated, because people with lupus are
at an increased risk for heart disease. In fact, cardiovascular diseasenot
lupus itselfis the number one cause of death in people with lupus.
Furthermore, medications used in lupus treatment, especially corticosteroids
such as prednisone, can raise blood pressure, blood glucose, cholesterol, and
triglyceride levels, exacerbating the risk factors for cardiovascular disease in
people with lupus.

A fasting lipid profile is performed only when a patient is fasting (i.e., has not
eaten since midnight of the previous night). Fasting ensures an accurate
reading of your baseline total cholesterol, HDL, LDL, and triglyceride levels.
However, please understand that it is alright to take your medications with
water upon the day you are fastingwater does not affect the fasting lipid
profile.

Total Cholesterol: Cholesterol is a fatty substance made in the body and


absorbed from certain foods that is essential in your bodys normal
processes. It plays an important role in the membranes of your cells, is used
to make hormones, and helps form the bile acids needed for your body to
obtain nutrients from food. Your total cholesterol is a measurement of both
types of cholesterolLDL and HDLand should be below 200 mg/dL. Total
cholesterol levels above 240 mg/dL are considered dangerously high,
especially in people with additional risk factors for cardiovascular disease,
such as smoking, obesity, or family history. If your total cholesterol level is
above 200 mg/dL, your doctor will most likely recommend that you follow a
diet low in saturated fats and cholesterol and begin a moderate exercise
regimen. If diet and exercise alone are not enough to control your cholesterol,
she/he may prescribe a medication called a statin to help lower your
cholesterol levels.

Low Density Lipoproteins (LDL): Cholesterol circulates in the body in


complex molecules called lipoproteins. Low density lipoproteins (LDL) are
sometimes known as bad cholesterol, because they can deposit excess
cholesterol in your arterial walls, restricting blood flow and causing a
condition known as atherosclerosis. If arteries become blocked, a person can
suffer heart attack, stroke, or other complications. LDL levels above 100
mg/dL are considered to be above the optimal range. If you have other risk
factors for heart disease, such as a history of smoking, low HDL levels, high
blood pressure, diabetes, or a personal or family history of cardiovascular
disease, you should aim for lower LDL levels.

High Density Lipoproteins (HDL): High density lipoproteins (HDL) are


known as good cholesterol because they help to move cholesterol out of
the body by carrying it to the liver where it is processed for excretion. HDL
levels less than 40mg/dL are associated with an increased risk of heart
disease, but a good HDL level is above 60mg/dL.

Protein

A comprehensive metabolic panel will also check the levels of certain


proteins in your blood. Specifically, the test checks for albumin levels and
total protein levels.

Albumin: Albumin is a small protein made in the liver that constitutes the
major protein in blood serum. Albumin performs many functions in your body,
including nourishing tissues, transporting various substances through the
body (hormones, vitamins, drugs, and ions), and preventing fluid from leaking
out of your blood vessels. Albumin concentration will drop if a person suffers
from liver damage, kidney disease, malnourishment, serious inflammation, or
shock. Abumin levels allow your doctor to assess for or monitor liver or
kidney disease due to lupus and other factors.

Total Protein: In addition to albumin, your blood serum also contains a


protein called globulin. In fact, globulin is actually a class of proteins that
includes enzymes, antibodies, and hundreds of other proteins. A total protein
test measures the combined amount of these proteins in your blood. An
albumin to globulin (A/G) ratio is also computed. A persons total protein level
gives information about kidney damage, liver damage, and nutritional health.
If your total protein falls outside of the normal level, your doctor will most
likely order other tests to assess for liver or kidney function.

Electrolytes

Electrolytes are ions (electrically charged chemicals) in the blood and other
body fluids. The concentration of electrolytes in your body depends on
adequate intake of nutrients, proper absorption of nutrients by the intestines,
and proper kidney and lung function. Abnormal electrolyte concentrations
can indicate abnormalities in certain organs and bodily processes. For
example, retention of sodium, bicarbonate, or calcium can indicate problems
with kidney function. Hormones also help to control electrolyte
concentrations, so abnormal electrolyte levels can also reveal certain
hormone deficiencies or problems with certain hormone-regulating glands or
organs. Some of the electrolytes measured in a comprehensive metabolic
panel are explained below.

Sodium (Na+): Sodium helps to regulate your bodys water balance and
plays an important role in proper heart rhythm, blood pressure, blood volume,
and brain and nerve function. Hypernatremia refers to having too much
sodium in the blood; this can occur, for example, due to a high-salt diet. Too
much sodium in your blood can cause high blood pressure, among other
things. Hyponatremia refers to having too little sodium in the blood.
Hyponatremia can cause confusion, restlessness, anxiety, weakness, and
muscle cramps. Sodium levels in the blood are regulated by a hormone called
aldosterone that is secreted by the adrenal glands. Aldosterone works to
regulate sodium levels by increasing your kidneys reabsorption of sodium
ions.

Potassium (K+): Potassium plays a role in regulating the acid-base


chemistry and water balance in your blood and body tissues. It also helps
your body to synthesize proteins and make use of carbohydrates for fuel.
Potassium is essential for normal muscle growth and helps sodium and
calcium to maintain normal hearth rhythm and regulate the bodys water
balance. Potassium also helps your muscles to contract and your nerves to
send impulses. Potassium levels may be low if an individual is on a diuretic
(fluid pill) such as hydrochlorothiazide (HCTC) or furosemide (Lasix). Blood
potassium levels that are too high or low may lead to muscle weakness and
cramping; very low levels may cause irregularities in heartbeat. Like sodium
levels, potassium levels in the blood are regulated by aldosterone, which
promotes potassium loss from your kidneys.

Calcium (Ca2+): Most people recognize calcium as a part of bones and


teeth, but calcium plays many other roles in the body, such as regulating
heartbeat, transmitting nerve impulses, contracting muscles, and helping
blood to clot properly. Blood calcium levels are regulated by parathyroid
hormone, which is secreted by the parathyroid gland, and calcitonin, which is
secreted by the thyroid gland. Since lupus causes an increased risk of
osteoporosis and corticosteroid (e.g., prednisone) use can elevate this risk,
most people with lupus should take calcium and vitamin D supplements to
help maintain adequate bone density. Medications called bisphosponates may
be added to help with bone integrity if osteoporosis is detected. However, it is
important that you realize that a blood calcium test measures the amount of
calcium in the blood, not the bones. For an adequate measurement of bone
health, you will need to obtain a DEXA scan every 2 years.

Chloride (Cl-): Chloride ions help your body in maintaining proper pH and
fluid balance. It also secreted by the stomach during digestion. Excessive
sweating, vomiting, or diarrhea can cause chloride levels to drop. Low
chloride levels may alter the pH of your blood, cause dehydration; they may
also cause you to lose potassium.

Carbon dioxide (CO2): This test measures the amount of carbon dioxide
(CO2) in the blood, which is present in the form of CO2, bicarbonate (HCO3-),
and carbonic acid (H2CO3). These three forms are involved in the equilibrium
that maintains the pH of your blood (7.35-7.45). Bicarbonate also works with
other electrolytes to maintain a certain charge balance in your cells. The
concentration of carbon dioxide in your blood is maintained by your lungs and
kidneys. High or low levels of CO2 may prompt your doctor to order other
tests to check your kidney and lung function, blood gases, or fluid retention.

Liver Tests

Lupus and some of the medications used to treat lupus can affect the liver. In
addition, factors such as excessive alcohol intake or viral hepatitis can affect
the liver in people with lupus, just as they can in the normal population.
Certain tests can be performed as part of a comprehensive metabolic panel
to give insight into the function of your liver. In addition, your doctor may
order a test called a liver panel if she/he suspects that you have symptoms
of a liver disorder. Usually these tests measure certain liver enzymes, namely
alkaline phosphatase (ALP), alanine amino transferase (ALT), and aspartate
amino transferase (AST). Bilirubin, a waste product of the liver that is stored
in the gall bladder, is also measured. These values can be used by your
doctor as a screening or monitoring tool for liver involvement. About 30-60%
of lupus patients experience abnormal liver function tests; some have no
symptoms of liver disorder. Generally, increased levels correlate with
increased activity, but other factors can contribute to elevated levels of liver
enzymes in the blood. For example, NSAIDs, acetaminophen (Tylenol), and
aspirin can cause liver enzyme values to increase, especially in people with
lupus. If your doctor notices abnormal liver enzyme levels, she/he may ask
you to undergo additional tests for hepatitis.

The liver enzymes and substances detected in a comprehensive metabolic


panel are explained in more detail below.

Alkaline phosphatase (ALP): Alkaline phosphatase (ALP) is an enzymea


protein that helps to bring about chemical reactions in your bodyfound
mainly in your liver and bones. High levels of ALP in the blood may indicate
bone or liver abnormalities. If high ALP values are accompanied by high
values of other liver enzymes and bilirubin, then the test suggests liver
involvement. Certain ratios of liver enzymes can also indicate more specific
conditions. Children usually have higher ALP levels than adults because their
bones are still growing.

Alanine amino transferase (ALT): Alanine amino transferase (ALT) is


another enzyme found mainly in the liver. Smaller quantities can also be
found in your kidneys, heart, and muscles. Levels of this enzyme are usually
assessed in conjunction with readings for other liver enzymes to determine or
monitor liver involvement. Very high levels of ALT may indicate acute
hepatitis.

Aspartate amino transferase (AST): Aspartame amino transferase (AST)


is an enzyme found mainly in the liver, heart, and muscles. AST is released
into the blood by injured liver or muscle cells but is used primarily to detect
liver damage. [Another enzyme called creatine kinase (CK or CPK) is a better
indicator of heart or muscle damage.] Levels of AST are usually viewed
alongside other liver enzymes to assess for liver damage. Like ALT, very high
levels of AST may suggest acute hepatitis.

Bilirubin: Bilirubin is a yellow-brown substance formed when the liver breaks


down old red blood cells. Too much bilirubin can be a sign that the liver
cannot adequately remove bilirubin from the system due to blockage (e.g.,
gallstones, tumors), cirrhosis, or acute hepatitis. Elevated bilirubin can also
indicate hemolytic anemia, a reduction in red blood cells due to abnormal
breakdown of red blood cells (hemolysis). Hemolytic anemia can be inherited
or acquired; about 10-15% of people with lupus develop autoimmune
hemolytic anemia. Hemolytic anemia causes red blood cells to have a
shortened lifespan in the blood, and since bilirubin is a product of old red
blood cells, it accumulates in the body faster than it can be eliminated.
[Other tests called the Coombs test, haptoglobin count, and reticulocyte
count are better diagnostic tests for hemolytic anemia.] Several inherited
conditions, such as Gilberts syndrome, can also cause a person to have too
much bilirubin. These conditions may be serious or benign. Often a buildup of
bilirbubin is accompanied by a yellowing of the skin called jaundice.
Thyroid Tests

The thyroid is a gland in your neck associated with your metabolismthe


processes by which your body makes use of energy. Autoimmune thyroid
disease can occur in people with lupus, as can other thyroid conditions.
Usually, thyroid conditions cause the gland to release too much or too little
hormone. Your doctor may order tests to detect the level of thyroid hormones
in the blood, especially if you experience significant weight loss or gain,
sweating, acute sensitivity to hot or cold, fatigue, or other symptoms. These
tests can also help your doctor monitor the effectiveness of thyroid
treatment. Tests for thyroid hormones are explained below in greater detail.
Your doctor may request additional tests, such as tests for thyroid antibodies,
to learn more about your condition.

Thyroid stimulating hormone (TSH): Thyroid stimulating hormone (TSH)


is a hormone released by the pituitary gland that signals the thyroid to
release its hormones (T3 and T4) when levels in the blood get low. Together,
TSH, T3, and T4 are part of a negative feedback loop that keeps levels of
thyroid hormones constant in the blood. Abnormal levels of TSH in the blood
can suggest a problem with the pituitary gland, such as a tumor, but this is
unlikely. More often, high or low TSH levels indicate problems with the thyroid
gland. The thyroid may not be responding to stimulation by TSH, or it may be
releasing too much T3 and T4. Underactive thyroid (hypothyroidism) is more
common in lupus, but overactive thyroid (hyperthyroidism) can also occur.
Both of these conditions can be dangerous if not properly treated.

T4 and T3: Thyroid hormone contains thyroxine (T4, 90%) and


triidothyronine (T3, 10%). The primary role of these substances is to regulate
your bodys metabolism. Abnormal levels of thyroid hormone can indicate
hypo- or hyperthyroidism.

Urinalysis

A complete urinalysis evaluates several different aspects of your urine


through physical, chemical, and microscopic examination. In lupus
treatment, a urinalysis is often used to monitor protein leakage and identify
and assess urinary tract infections (UTIs). Most people with kidney lupus
(lupus nephritis) will have an abnormal urinalysis. Protein, urine casts
(especially red blood cell casts), red blood cells, or white blood cells in the
urine can indicate serious kidney involvement; leukocyte esterase amy
indicate a bladder infection.

Urine samples can be given at any time while at the doctors office. A urine
culture is performed to assess for a bladder infection and to determine
appropriate antibiotics. Before giving a urine sample, ask a medical
professional to counsel you on how to prevent contamination. Several
analytical elements of the complete urinalysis are explained below.

Physical Examination / Macroanalysis

In this portion of the analysis, the color, clarity, and concentration of the
urine are evaluated. Abnormal colors can result from disease, certain foods,
or contamination, so the physical examination is generally viewed as a crude
assessment. Light or dark coloration also suggests how much water is being
excreted. The clarity of urine is measured as either clear, slightly clear,
cloudy, or turbid. Urine clarity, like urine color, suggests that substances may
be present in the urine; for example, turbid urine suggests the presence of
protein or excess cellular material. However, accurate conclusions regarding
the origin of the urine clarity cannot be drawn until further chemical and
microscopic tests are performed. The physical examination also includes
specific gravity, which measures the concentration of the urine sample.
Specific gravity compares the concentration of urine to that of water (1.000).
Usually it is better for the urine given in a sample to be more concentrated;
this allows the laboratory to more accurately detect substances being
excreted by your body. If your urine is very dilute (i.e., you have been
drinking lots of water or receiving fluid via IV), you may be asked to give
another urine sample.

Chemical Analysis
The chemical examination measures several features of the urine. Most
laboratories use chemical test strips (dipsticks) that change colors when
dipped into the urine. Either the laboratory technician or an automated
instrument will then read the reaction color for each test pad to determine
the result for each test. The use of automated instruments helps to eliminate
discrepancies that arise with human interpretation.

pH: Usually, the pH of urine is between 4.5 and 8.0. The kidneys regulate this
acid-base chemistry by reabsorbing sodium and secreting hydrogen and
ammonium ions. When the body retains excess sodium or acid, urine
becomes more acidic (i.e., the pH is lower). Highly acidic urine can occur with
uncontrolled diabetes, diarrhea, starvation, dehydration, and certain
respiratory diseases. When your body retains excess base, your urine
becomes more basic, or alkaline (i.e., the pH is higher). This can occur with
urinary tract infections and certain kidney and lung conditions. Certain foods
can also alter the pH of your urine. For example, eating excessive protein or
cranberries can make your urine more acidic, whereas eating a low-
carbohydrate or vegetarian diet can make your urine more basic. Sometimes
people are asked by their doctors to regulate the pH of their urine through
diet in order to manage certain diseases or medications. For example, kidney
stones can occur if urine pH is too high or too low.

Protein: Excessive protein in the urine (proteinuria) is a sign of kidney


involvement in lupus. Usually, your kidneys prevent protein from passing
from your blood into your urine: loops of capillaries (glomeruli) that filter
blood allow small particles to pass into the urine while retaining larger
particles, such as protein, and kidney tubules reabsorb the smaller proteins
that were able to escape. Large amounts of protein in the urine suggest that
these glomeruli and tubules are inflamed or damaged in some way.

If there is a large amount of protein in the urine, your doctor may request
that you give a 24-hour urine sample or obtain a random protein to
creatinine ratio. These two tests are used to monitor lupus affecting the
kidneys (lupus nephritis).
Glucose: Your urine should not contain glucose. If it does, your doctor will
order further bloodwork and urine tests to determine the cause. Glucose in
the urine is called glucosuria; it can occur in people with diabetes that is not
properly regulated with insulin, in people with kidney problems that affect the
absorption of glucose, in pregnant women, and in people with liver
abnormalities or hormonal disorders.

Ketones: Ketones in the urine (ketonuria) indicate that your body is


metabolizing its fat reserves instead of carbohydrates to obtain energy. This
can occur in people on low-carbohydrate diets, people who are malnourished,
or people who have a problem properly metabolizing carbohydrates (e.g.,
people with diabetes). It can also occur with excessive exercise, loss of
carbohydrates due to vomiting, or exposure to cold. In people with diabetes,
ketonuria may indicate insufficient management with insulin.

Blood: The chemical examination of urine also measures the amount of red
blood cells in the urine sample. The presence of red blood cells in the urine is
known as hematuria, and the presence of hemoglobin (from red blood cells) is
known as hemoglobinuria. Usually people have very small amounts of red
blood cells in their urine, but even a minute increase can indicate a problem,
such as a disease of the kidney or urinary tract, trauma, medications,
smoking, or intense exercise (e.g., running a marathon). When the chemical
test for blood in the urine is negative but the microscopic assessment shows
the presence of red blood cells, the laboratory will usually check for the
presence of vitamin C, which can interfere with test results. [It is important
to also note that contamination of the urine sample with menstrual
blood or hemorrhoids cannot be distinguished from the presence of
red blood cells in the sample. Therefore, it is very important to tell
your physician if you are menstruating or are experiencing any other
condition that could contaminate your urine sample. It is also very
important that you speak to your lab technician about proper aseptic
technique when giving a urine sample.]
Leukocyte Esterase: Leukocyte esterase is an enzyme present in your
white blood cells. Therefore, the presence of this substance in the urine
indicates the presence of white blood cells (leukocyturia). White blood cells in
the urine may indicate inflammation of the kidneys or urinary tract due to
bacterial infection. It is important to note, however, that contamination of the
urine can also cause the presence of white blood cells in the urine, so
remember to practice proper aseptic technique when giving the sample.

Nitrite: Bacteria can convert nitrate to nitrite; therefore, the presence of


nitrite in the urine usually indicates a bacterial infection (i.e., a urinary tract
infection). However, not all bacteria can convert nitrate to nitrite, so it is
possible to have a urinary tract infection while also having a negative nitrite
test.

Bilirubin: Bilirubin is made by the liver from old red blood cells; it is then
processed by the intestine and excreted from the body. Therefore, healthy
individuals do not have bilirubin in their urine. The presence of bilirubin in the
urine indicates that the liver is allowing the substance to leak back into the
blood. This can be an early indication of liver disease, even when other
symptoms, such as jaundice, are not present.

Microscopic Analysis

The microscopic examination uses a microscope to identify and count cells,


crystals, bacteria, mucous, and other substances that may be present in the
urine. The amount of a substance present is reported one of two ways: as a
count with the microscope strength used to view the substance [per low
power field (LPF) or per high power field (HPF)], or as an approximate
amount (rare, few, moderate, or many).

Red Blood Cells: The microscopic examination looks at how many red blood
cells are present per HPF. As discussed above, the presence of red blood cells
in the urine can indicate a problem, such as a disease of the kidney or urinary
tract, trauma, medications, smoking, or intense exercise (e.g., running a
marathon). However, contamination of the urine sample with menstrual blood
or hemorrhoids cannot be distinguished from the presence of red blood cells
in the sample. Therefore, it is very important to tell your physician if you are
menstruating or are experiencing any other condition that could
contamination your urine sample. It is also very important that you speak to
your lab technician about proper aseptic technique when giving a urine
sample.

White Blood Cells: A high number of white blood cells in the urine indicates
inflammation of the kidneys or urinary tract. Like the test for red blood cells,
this test can be misread if the sample is contaminated; in this instance,
contamination can occur from vaginal secretions, which are high in white
blood cells. Therefore it is important that you speak to your lab technician
about proper aseptic technique before giving a urine sample.

Epithelial Cells: The tissue that lines the surfaces of cavities and structures
in your body is called epithelial tissue. In healthy individuals, epithelial cells
from the bladder and external urethra are normally present in the urine in
small amounts. However, the amount of epithelial cells in the urine increases
when someone has a urinary tract infection or some other cause of
inflammation. Your doctor will evaluate the source of the problem by
evaluating the type of epithelial cells that are present. For example, the
presence of renal tubular epithelial cells (from your kidneys) may indicate
kidney involvement. The presence of squamous epithelial cells may indicate
contamination of the urine specimen.

Casts: Casts are formed in the tubules of they kidney when the tubules
secrete a protein called Tamm-Horsfall protein. The origin of the casts causes
them to take on a tubular or hotdog-like shape. These casts are known as
hyaline casts and can be present in normal adults on the order of 0-5 per LPF.
Strenuous exercise can cause more hyaline casts to be present. However,
casts made from red or white blood cells indicate problems in the kidney. Red
blood cells that stick together and form red blood cell casts usually indicate
problems with the glomeruli, tiny ball-shaped structures in your kidneys that
help filter blood and prevent the loss of valuable substances, such as blood
cells and proteins. White blood cells casts indicate inflammation in the kidney.
Cellular casts that remain in the nephron of your kidney for a long time
before they are flushed out become granular casts and eventually waxy
casts.

Bacteria: Bacteria in your urine can suggest infection, especially if you have
other suggestive symptoms. If your doctor suspects that you may have a
urinary tract infection, she/he will most likely order a culture or count of the
bacteria. However, bacteria on the skin can also contaminate the urine
sample and skew the results, so it is very important that you understand
proper aseptic technique when giving a urine sample.

Crystals: Crystals can be present in the urine of healthy individuals; these


crystals form when the pH, solute concentration, and temperature of your
urine are within a specific range. If these crystals are made of substances
that are supposed to be in urine, such as calcium oxalate or phosphate, then
they are considered to be normal. Crystals made of substances that are not
usually present in urine, such as cystine, tyrosine, or leucine (amino acids),
are uncommon and usually indicate liver disease or some other abnormal
process

Erythrocyte Sedimentation Rate (ESR)

Erythrocyte is another word for red blood cell. The erythrocyte (or, red blood
cell) sedimentation rate (ESR) is a test that measures the amount of
inflammation in your body. For the test, blood is drawn from a vein in your
arm into a special tube. The rate of fall (sedimentation) of red blood cells is
then measured, as the red blood cells become sediment at the bottom of the
tube, leaving blood plasma at the top of the column. The results are reported
in terms of how many millimeters of clear blood plasma are present at the
top of the column after one hour. Usually red blood cells fall slowly so that
there is little clear plasma left at the top. However, when the blood contains
higher amounts of certain proteins involved in inflammation, namely
fibrinogen and immunoglobulins (antibodies), the red blood cells fall more
rapidly, resulting in an increased ESR. Therefore, sedimentation rate
increases with more inflammation. A normal ESR is usually about 0-20
millimeters per hour in females and 0-12 millimeters per hour in males. The
ESR is nonspecific, meaning that it does not tell your doctor exactly where
the inflammation is occurring in your body and is thus not a very strong
indicator of lupus activity.

C-reactive Protein (CRP)/Westergren Sedimentation Rate

Like the erythrocyte sedimentation rate, the C-reactive protein (CRP) test
measures inflammation. However, CRP usually changes more rapidly than
ESR because it is made by the liver and secreted hours after the beginning of
infection or inflammation. CRP plays a part in your immune response by
interacting with your bodys complement system. The CRP is non-specific,
meaning it cannot give your doctor information about where inflammation is
occurring in your body. However, the amount of CRP can give an idea as to
the degree of inflammation your body is experiencing, and it is used by
doctors in lupus treatment to monitor flares and to assess how well your
medications are working. It is important to realize, though, that a low CRP
value does not necessarily mean that an individual is experiencing no
inflammation; a low CRP can be seen in lupus patients with active
inflammation. An elevated CRP can also be seen after someone has a heart
attack, surgical procedure, or infection.

High Sensitivity C-Reactive Protein (HS CRP)


In apparently healthy individuals, studies have shown that C-reactive protein
(CRP) can be an indicator of the risk of cardiovascular disease (CVD), since
certain types of CVD, namely atherosclerosis, are known to involve
inflammation. A high sensitivity test (high sensitivity C-reactive protein, or
HS CRP) is used to evaluate this risk, because the level of CRP in the blood is
low. The high sensitivity CRP is important because studies have shown that
lupus patients have higher levels of atherosclerosis than the general
population. However, the HS CRP can reflect many things in lupus patients
besides lupus activity and/or ones risk of heart attack.
For the HS CRP test, blood is taken from a vein in your arm and mixed with a
substance called an antiserum. The antiserum contains a specific substance
that is able to detect the CRP. The American Heart Association and Centers
for Disease Control and prevention maintain that a high-sensitivity CRP of
less than 1.0 mg/L suggests a low risk for CVD, 1.0-3.0 mg/L suggests an
average risk, and a CRP above 3.0 mg/L suggests a high risk.

Creatine Phosphokinase (CPK)

Creatine phosphokinase (a.k.a., creatine kinase, CPK, or CK) is an enzyme (a


protein that helps to elicit chemical changes in your body) found in your
heart, brain, and skeletal muscles. When muscle tissue is damaged, CPK
leaks into your blood. Therefore, high levels of CPK usually indicate some
sort of stress or injury to your heart or other muscles. To test CPK, blood is
drawn from a vein in your arm

In the hospital, a persons CK-MB level is often checked when they exhibit
signs of heart attack. However, in lupus treatment, an elevated CPK may
suggest muscle inflammation due to disease activity or an overlapping
condition. CPK levels can also be high after strenuous exercise, so your
doctor may wish to recheck your CPK after several days of rest. If your CPK is
high with no exercise or remains high with rest, your doctor may order
additional tests to determine which type (isoenzyme) of CPK is elevated. This
information will help her/him to determine the source of the damage
(skeletal muscles, heart, or brain). Certain medications, such as statins, can
cause increases in CPK, so be sure to tell your doctor about any medications
you currently take.

Coombs Test

The Coombs test is used to detect antibodies that act against the surface of
your red blood cells. The presence of these antibodies indicates a condition
known as hemolytic anemia, in which your blood does not contain enough
red blood cells because they are destroyed prematurely. A healthy red blood
cell lives for about 120 days; in people with hemolytic anemia, red blood
cells are destroyed long before the 120-day marker. Sometimes, bone
marrow can compensate for the early destruction of red blood cells by
working overtime to make more of them. However, this extra effort may not
be enough to combat hemolytic anemia.

Hemolytic anemia can either be inherited genetically or acquired. An


acquired form, autoimmune hemolytic anemia (AIHA), is present in about
10% of people with lupus and results from an immune system attack on your
red blood cells. People with AIHA may experience weakness, dizziness,
fevers, and a yellowed complexion. Treatment calls for high doses of steroids
such as prednisone, which may be supplemented with immunosuppressive
medications such as azathioprine (Imuran).

There are two types of Coombs tests: direct and indirect. The direct Coombs
test, also known as the direct antiglobulin test, is the test usually used to
identify hemolytic anemia. [The indirect Coombs test is used only in prenatal
testing of pregnant women and in testing blood prior to a transfusion.] For
the direct Coombs test, blood is drawn from the vein in your arm and then
washed to isolate your red blood cells. The red blood cells are then
incubated (combined in a controlled environment) with a substance called
Coombs reagent. If the red blood cells clump together (a process called
agglutination), then the Coombs test is said to be positive.

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