Waldenstrom`s

Transcription

Waldenstrom`s

Waldenstrom’s Macroglobulinemia
Medical Tests
The IWMF Vision Statement
Support everyone affected by Waldenstrom's macroglobulinemia while advancing the search for a cure.
The IWMF Mission Statement
To offer mutual support and encouragement to the Waldenstrom's macroglobulinemia community and others with an
interest in the disease.
To provide information and educational programs that address patients' concerns.
To promote and support research leading to better treatments and ultimately, a cure.
Published by the International Waldenstrom’s Macroglobulinemia Foundation (IWMF)
This information has been provided by the IWMF at no cost to you. Please consider joining and/or contributing to the IWMF to
enable us to continue to provide materials like this to support research toward better treatments and a cure for Waldenstrom’s
macroglobulinemia. You may join and/or contribute at our website, www.iwmf.com, or you may mail your contribution to:
6144 Clark Center Avenue, Sarasota, FL 34328.
IWMF is a 501(c)(3) Tax Exempt Non-Profit Organization, Fed ID #54-1784426.
2007
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Table of Contents
PREFACE ............................................................................................................................................................................... 1
BLOOD TESTS FOR WALDENSTROM PATIENTS ................................................................................................................... 2
INTRODUCTION ............................................................................................................................................................... 2
MAJOR BLOOD TESTS FOR WALDENSTROM’S MACROGLOBULINEMIA ..................................................................................... 3
IMMUNOGLOBULIN TESTS ................................................................................................................................................. 9
INTRODUCTION ............................................................................................................................................................... 9
TESTS FOR MEASUREMENT OF IMMUNOGLOBULINS ............................................................................................................ 9
OTHER IMPORTANT TESTS FOR WALDENSTROM’S PATIENTS WITH RELATED INFORMATION ..................................... 15
URINE TESTS ................................................................................................................................................................... 15
BONE MARROW BIOPSY................................................................................................................................................... 15
TESTS FOR SELECTED CONDITIONS IN WALDENSTROM’S MACROGLOBULINEMIA ....................................................... 17
AMYLOIDOSIS ................................................................................................................................................................ 17
ANEMIA ........................................................................................................................................................................ 17
COLD AGGLUTININ DISEASE ........................................................................................................................................... 18
CRYOGLOBULINEMIA ....................................................................................................................................................... 18
PERIPHERAL NEUROPATHY ................................................................................................................................................. 18
VISUAL DISORDERS .......................................................................................................................................................... 19
APPENDIX 1: GLOSSARYOF MEDICAL TERMS RELATING TO TESTS ................................................................................................ 20
APPENDIX 2: MEDICAL PROCEDURES ..................................................................................................................................... 32
APPENDIX 3: LABORATORY PROCESSES ........................................................................................................................... 39
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PREFACE
This booklet was prepared for the individual who has a general interest in Waldenstrom’s macroglobulinemia (WM).
The general objective in mind is the development of a ready, simple reference booklet of medical terms and tests,
with particular reference to IgM measurement and the Complete Blood Count (CBC) laboratory test, as well as a
comprehensive glossary of selected terms from the clinical and research world of WM.
No glossary of terms in the rapidly advancing world of medical science stays current and up-to-date for very long;
however we hope that this booklet builds on a foundation of ever-expanding knowledge for the interested patient,
caregiver, or anyone curious about WM for that matter.
Guy Sherwood, MD, CCFP, ABHM March, 2007
Copyright 2007 IWMF and Guy Sherwood, MD
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BLOOD TESTS FOR WALDENSTROM PATIENTS
INTRODUCTION
The Complete Blood Count (CBC) is a commonly ordered group of tests that evaluate the red blood cells, white blood cells, and
platelets. The CBC is an automated test, can be done rapidly, and occasionally requires definitive evaluation by a hematologist
under direct microscopy. The CBC measures hematocrit, hemoglobin, the volume (MCV) of each red blood cell (RBC),
hemoglobin per RBC (MCH), concentration of hemoglobin in the red blood cell (MCHC), number of RBCs, white blood cells
(WBCs), and platelets; a differential count or “diff ” counts the lymphocytes, monocytes, eosinophils, basophils, and neutrophils. If
the automated differential is abnormal, a manual differential is performed to verify the results. The manual differential is labor
intensive and involves the preparation of a microscope slide and visually counting the cells under a microscope.
Blood is a fluid tissue that performs many important vital functions in the human body. The most important of these functions is the
transport and delivery of oxygen from the lungs to the body’s tissues and the subsequent transport of waste gases, predominantly carbon
dioxide, from the body’s tissues to the lungs for elimination. The blood performs other vital functions such as transport and delivery of
immune system cells, coagulation (clotting), participation in the acid-base and fluid balance systems of the body, regulation of body
temperature, transport of nutrients and hormones to body tissues, and the transport to, and ultimate disposal of, wastes by the
kidneys, lungs, and skin.
Blood is approximately three times thicker than water, is slightly salty in taste, and is very slightly alkaline, or basic (pH 7.4). The
arteries carry bright red oxygen-rich blood from the lungs to the tissues, and the veins carry dark red oxygen-poor blood from the
tissues back to the lungs.
The blood has two major components: the plasma, which is the clear, straw-colored fluid portion that contains proteins, enzymes,
nutrients, and other dissolved molecules; and the formed elements that are the red blood cells, white blood cells, and platelets.
This section will review in greater detail:
1. The Red Blood Cells: including the Red Blood Cell Count; Hematocrit; Total Hemoglobin; Red Cell Indices (MCV, MCH, and
MCHC); as well as other selected relevant tests not ordinarily found in a CBC such as the Red Cell Distribution Width
(RDW), Reticulocyte Count and Erythrocyte Sedimentation Rate.
2. The White Blood Cells: including the White Blood Cell Count and the White Blood Cell Differential.
3. The Platelets: Platelet Count and Mean Platelet Volume.
This section will also include the comparative units of measurements used in various countries. The metric system is in
virtually universal use in health care systems and particularly in laboratory assays worldwide; the major differences being the
concentration nomenclature used.
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MAJOR BLOOD TESTS FOR WALDENSTROM’S MACROGLOBULINEMIA
1. The Red Blood Cells
Red Blood Cell Count (RBC)
The most vital role of the red blood cell is to carry oxygen from the lungs to the tissues and to subsequently transport waste gases from
the tissues for expulsion in the lungs.
Why is this test done?
1. To evaluate the number and size(s) of red blood cells.
2. To determine the hemoglobin content and condition of red blood cells.
3. To assist in diagnosing health problems related to blood.
What are the normal results?
1. Men: 4.2 to 5.4 million RBCs per microliter of blood (4.2 to 5.4 x 1012 /L).
2. Women: 3.6 to 5.0 million RBCs per microliter of blood (3.6 to 5 x 1012 /L).
What is the significance of an abnormal result?
1. A decreased red blood cell count may indicate anemia, fluid overload, or severe bleeding.
2. An elevated count may indicate polycythemia.
3. Further tests are required to determine the exact diagnosis.
4.
Hematocrit
This test simply measures the percentage (%) of red blood cells, or hematocrit, in a blood sample. The results vary by sex and age of the
patient, with younger individuals such as infants and pre-teens having lower values.
1. To help diagnose blood disorders.
2. To help calculate the volume and concentration of blood cells.
1. Men: 42% to 54%.
2. Woman: 38% to 46%.
1. A low hematocrit % may indicate anemia, fluid overload, or massive blood loss.
2. A high hematocrit % may indicate polycythemia, dehydration, or other conditions.
Hemoglobin
The hemoglobin (Hgb) molecule is the iron-containing metallo- protein in red blood cells. Its purpose is to carry oxygen in the
blood. Hemoglobin makes up 97% of the dry weight of the RBC. The hemoglobin level, part of the CBC test, measures the amount of
hemoglobin per volume of whole blood.
1. To detect anemia or polycythemia or to assess response to various therapies.
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2. To assist in the calculation o f additional information for a complete blood count.
1. The hemoglobin concentration varies depending on the type of sample obtained (capillary finger sample, central
circulation via a central line, or most commonly peripheral veins). Hgb values also depend on the person’s sex, and the
maximum value declines with the person’s age.
2. Men: 14 to 18 g/dL or 140 to 180 g/L.
3. Women: 12 to 16 g/dL or 120 to 160 g/L.
1. Low hemoglobin values may be indicative of anemia, recent blood loss, or fluid overload.
2. Elevated hemoglobin values are commonly seen in polycythemia or dehydration.
Red Cell Count Indices
The red cell indices provide important information about the size (MCV), hemoglobin weight (MCH), and hemoglobin level
(MCHC) of an average red cell.
1. The information is of importance when diagnosing and evaluating anemia.
1. MCV – mean corpuscular volume – the ratio of the hematocrit to the red blood cell count: 80 to 100 fL.
2. MCH – mean corpuscular hemoglobin – the weight of the hemoglobin in an average red blood cell: 26-32 pg.
3. MCHC – mean corpuscular hemoglobin concentration – the % level of hemoglobin in a given volume of red blood cells:
30% to 60% g/dL.
1. MCV calculates the average size of the RBC and notes if they are microcytic (small), macrocytic (big), or normocytic (normal).
Small RBCs are commonly seen in iron deficiency anemia, whereas large RBCs are typical of some vitamin deficiency states.
MCV is key value is evaluating anemia.
2. MCH will often yield clues to the state of hemoglobin synthesis. Low values are seen in states of chronic diseases, iron
deficiency anemia, etc.
3. MCHC values are helpful in distinguishing normochromic (normally colored) red cells from hypochromic (paler)
red cells, as is the case often in certain disease states.
Red Cell Distribution Width (RDW)
The RDW is the coefficient of variation of the normally Gaussian- shaped RBC volume distribution histogram, and is determined by
dividing the standard deviation of the MCV by the MCV and multiplying by 100 to convert the value to a percentage. Thus the
RDW provides a quantitative measure of variation in size of thecirculating RBC. See Reticulocyte count for further information.
1. A rather advanced test used to grossly evaluate the age- distribution of the red blood cell population.
1. 13.5% ± 1.5%.
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1. An increased result can often indicate a response to therapy for anemia, as young RBCs are being produced at a more rapid
rate than usual.
2. A low value will suggest a static population of RBCs, with not much variability in size (and age).
Reticulocyte Count
Reticulocytes are immature red blood cells. They are generally larger than mature red blood cells. One can assess effective RBC
production simply by measuring the reticulocyte count. The number of reticulocytes is expressed as a percentage of the total red cell
count. Generally, the higher the reticulocyte count, the higher the red cell distribution width (RDW).
1. To detect anemia or monitor its treatment.
2. To distinguish between different types of anemias.
3. To help assess blood loss or the bone marrow’s response to anemia.
1. Reticulocytes compose 0.5% to 2.0% of the red blood cell count.
1. A low reticulocyte count indicates low production of new red blood cells such as occurs in hypoplastic or pernicious
anemia. Bone marrow failure, aplastic anemia, myelodysplastic syndrome also produce low reticulocyte counts.
2. A high reticulocyte count demonstrates response to therapy for anemia, or the healthy bone marrow’s response to anemia or
blood loss.
Erythrocyte Sedimentation Rate (Sed Rate, ESR)
This test measures the rate at which erythrocytes (red blood cells) settle to the bottom of a special blood sample test tube during a
specific time period. The ESR is a sensitive but nonspecific test that is frequently the earliest indicator of disease when other tests
or physical signs are normal. The ESR commonly increases greatly in widespread inflammatory disorders; elevation may be prolonged in
localized inflammation or cancer.
1. To evaluate the condition of red blood cells.
2. To monitor inflammatory or malignant disease.
3. To aid in the detection and diagnosis of such diseases as tuberculosis and connective tissue disease.
1. Normal sedimentation rates range from 0 to 20 millimeters per hour.
2. The rates gradually increase with age; a reading of 30-40 may not be unusual for a person > 65 years of age.
1. The erythrocyte sedimentation rate increases in pregnancy, anemia, acute or chronic inflammation, tuberculosis,
rheumatic fever, rheumatoid arthritis, and some cancers.
2. Hyperviscosity syndrome in Waldenstrom’s macroglobulinemia, with its elevated IgM levels, can significantly increase the
ESR.
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2. The White Blood Cells
White Blood Cell Count (WBC)
Also known as leukocyte count, the white blood cell count (WBC) determines how many white blood cells are in a given volume of
blood. On any given day, the WBC may vary by as much as 2,000, be it due to strenuous exercise, stress, or infection. The number of
white blood cells may increase or decrease significantly in certain diseases, but as a diagnostic tool, the WBC is useful only when a
patient’s white cell differential and health status are considered.
1. To detect infection or inflammation.
2. To determine the requirement for further evaluations, such as the white blood cell differential or a bone marrow biopsy.
3. To monitor a patient’s response to cancer therapy.
1. Normal white blood cell counts range from 4,000 to 10,000 WBCs per cubic milliliter (mm3) of whole blood (4-10 x 109/L).
1. An elevated white blood cell count, referred to as leukocytosis, often indicates infection. Stressful events such as trauma, stoke, or
a heart attack can also transiently elevate the WBC. Certain hematological malignancies are characterized by elevated white
blood cell counts.
2. A low blood cell count, referred to as leukopenia, often indicates bone marrow problems. Toxic chemicals and viral
infections can cause a reduction in WBCs. Influenza, typhoid fever, measles, infectious mononucleosis, hepatitis, and rubella
can characteristically cause leukopenia.
White Blood Cell Differential
The white blood cell differential is used to evaluate the distribution of the five major types of white blood cells, or leukocytes:
neutrophils, eosinophils, basophils, lymphocytes, and monocytes. The differential also informs the clinician on the structure of these
cells, and permits a rapid overview of the immune system.
1. To evaluate the immune system and the body’s capacity to resist and overcome infection.
2. To determine the stage and severity of an infection.
3. To detect parasitic infections.
4. To detect and assess allergic reactions.
5. To detect and identify various types of leukemia.
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The following chart provides relative levels for the five types of white blood cells classified in the white blood cell differential:
TYPE OF CELL
NEUTROPHILS
LYMPHOCYTES
MONOCYTES
EOSINOPHILS
BASOPHILS
% OF CELLS
ABSOLUTE NUMBERS
48.0% to 77.0% 1.9-8.0 x 103/mm3 ( x 109/liter
16.0% to 43% 0.9-5.0
x 103/mm3 ( x 109/liter
)
0.6% to 9.6% 0.16-1.0
x 103/mm3 ( x 109/liter
)
0.3% to 7.0% 0.0-0.8
x 103/mm3 ( x 109/liter
)
0.3% to 2.0% 0.0-0.2
x 103/mm3 ( x 109/liter
)
)
Abnormal differential patterns provide evidence for a wide range of diseases and conditions. The following table summarizes how
diseases affect the white blood cell count:
CELL TYPE
DECREASED BY:
NEUTROPHILS
• Infections
• Trauma
• Metabolic disorders
• Stress response
• Inflammatory disease
• Marrow suppression
• Infections
• Liver & spleen disorders
• Collagen vascular disease
• Vitamin deficiency
EOSINOPHILS
• Allergic disorders
• Parasitic infections
• Skin diseases
• Malignancy
• Various other mechanisms.
• Stress response
• Trauma
• Cushing’s syndrome
BASOPHILS
• Leukemias
• Hemolytic anemias
• Hodgkin’s lymphoma
• Chronic inflammatory disease
• Kidney disease
• Infections
• Endocrine abnormalities
• Immune disorders
• Chronic lymphocytic leukemia
• Inflammatory diseases
• Hyperthyroidism
• Ovulation
• Pregnancy
• Stress
• Infections
• Collagen vascular disease
• Leukemias
• Lymphomas
• Immunosuppression
LYMPHOCYTES
MONOCYTES
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INCREASED BY:
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• Severe illness
• Corticosteroid therapy
• Immunosuppression
• Chemotherapy and others
• Malignancy
3. The Platelets
Platelet Count
Platelets, or thrombocytes, are the smallest formed elements in blood. They promote blood clotting after an injury. Aspirin (ASA,
ECASA) temporarily inhibits platelet function. A platelet count is one of the most important blood tests done.
1. To determine if blood clots normally.
2. To evaluate platelet function.
3. To assess the effects of chemotherapy or radiation therapy on platelet production.
4. To diagnose and monitor a severe increase in platelet count.
1. Normal platelet counts range from 130,000 to 400,000 platelets per mm3 of whole blood (130-400 x 109/L).
1. Low platelet counts (thrombocytopenia) can be caused by bone marrow suppression due to cancer or infection; folic
acid or vitamin B12 deficiency; trapping of platelets in an enlarged spleen; increased platelet destruction due to immune
disorders; or mechanical injury to platelets. A platelet count that falls below 50,000 can sometimes cause spontaneous
bleeding. When it drops below 5,000, fatal central nervous system bleeding or massive gastrointestinal hemorrhage is
possible.
2. A high platelet count (thrombocytosis) can be caused by severe bleeding, infection, cancer, iron-deficiency anemia, and
recent surgery, pregnancy, or spleen removal. A high count can also be caused by inflammatory disorders.
Mean Platelet Volume (MPV)
Additional information on platelet function is obtained from the mean platelet volume (MPV). In patients with normal bone
marrow function, platelet production will be stimulated as the platelet count begins to fall.
1. Measurement of the mean platelet size can often provide indirect evidence for the pathogenesis of thrombocytopenia (low
platelet count).
1. Normal platelet size is 7.2-11.1 fL.
1. Large platelets are present when there is thrombocytopenia stemming from increased platelet destruction.
2. Mean platelet volume rises because larger, newly made platelets will make up a higher proportion of the circulating
platelets.
3. An MPV that remains the same as the MPV for non-thrombocytopenic normal persons is not a normal finding in a
thrombocytopenic patient and suggests that failure of platelet production has contributed significantly to the pathogenesis
of the thrombocytopenia.
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IMMUNOGLOBULIN TESTS
INTRODUCTION
The immunoglobulin M (IgM) concentration and its increases or decreases are one of the key indicators of the malignant WM Bcell’s activity. Physicians utilize IgM levels as criteria for the diagnosis of WM and as a key marker for disease progression and
treatment efficacy. The IgM levels are an indicator of disease remission or relapse, and many will use the IgM levels and
more importantly the trend of IgM values over time as laboratory evidence of when symptoms may appear and may
indeed warrant therapy.
Monoclonal IgM is the immunoglobulin produced by our monoclonal WM B-cells. The monoclonal IgM molecules all have
the same molecular composition. (Note that in very rare occasions a patient with WM can have two types of monoclonal IgM
proteins from two different malignant WM B-cells. Some patients may even have monoclonal IgM from one cancerous WM cell
line and a second monoclonal immunoglobulin from a different class (usually IgG) from another cancerous WM cell line. Again,
this is quite rare, and a full discussion of this bi- clonality is beyond the scope of this booklet). The polyclonal IgM produced
by normal immune system B-cells has different molecular compositions based on which antigen the IgM targets. Much of the
polyclonal IgM is produced in response to foreign pathogens; whereas the monoclonal IgM of WM B-cells is secreted by the
tumor cells without chronic antigen stimulation. There is considerable debate as to what triggers these WMB-cells to secrete
IgM in the first instance, and some suggest that the WM IgM is released without any antigenic stimulation required at all.
The two most common laboratory methods for measuring IgM concentration in patient’s serum are nephelometry and
electrophoresis.
TESTS FOR MEASUREMENT OF IMMUNOGLOBULINS
1. Nephelometry
Nephelometry is a technique for measuring the “cloudiness” of a liquid such as drinking water. A more common term is “turbidity”
which is analyzed by a turbidimeter. Both the nephelometer and the turbidimeter measure the amount of light that is lost by scattering
while passing through the solution. Particles or large molecules such as the IgM protein suspended in the serum cause the light to be
scattered.
A turbidimeter has a detector that is in line with the light source directed through the serum or solution to be measured. Light
intensity is initially measured through a particle-free solution (usually distilled water) to obtain an accurate baseline reading. The
turbid sample in question is then measured, which results in a reduction in the light intensity that reaches the detector. The
reduction in light intensity is proportional to the amount and size of particles in the water. Calibrated standards are then used to
determine the amount of turbidity in the sample.
A nephelometer reads the light scattered from the particles, not the directed beam’s intensity once it has passed through the sample.
Therefore, a sample without particles will not scatter light and have a reading of zero. If particles are introduced or created by
precipitation on the sample, then light will be scattered and the intensity of the scattered light can be measured with a light sensor
or detector. The intensity of the light scatter is in direct proportion to the amount of suspended particles in the sample.
The nephelometer can be used to measure the immunoglobulins (IgA, IgG, and IgM) in our serum. IgE must be measured by more
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sensitive techniques such as radioimmunoassay or enzyme-linked immunoassay. The techniques varies somewhat, but generally the
serum sample is added to a quantity of distilled water and a specific antigen is subsequently added that will cause the desired
immunoglobulin to precipitate in the solution and form tiny particles. These Ig/antigen particles will scatter light. The amount of
light from the Ig/antigen precipitate can be compared to standardized values of known Ig concentration.
Both the monoclonal and polyclonal IgM will react with the antigen and precipitate to scatter light. Nephelometry cannot distinguish
how much of the total IgM is monoclonal. However, we know that under normal conditions, the polyclonal IgM of a normal immune
system varies from 50 to 300 mg/dL; we can therefore infer that a reading of 1000 mg/dL corresponds to a monoclonal IgM of 800
mg/dL (if we average a “normal” IgM value at 200 mg/dL). This is of course a gross oversimplification but is nonetheless satisfactory in
most instances as a static IgM value is not as important as a dynamic measurement of the IgM value trend over time.
1. To provide a rapid and accurate measurement of the serum concentration of IgA, IgG, and IgM.
1. IgA: 60 to 400 mg/dL, 0.6 to 4.0 g/L
2. IgG: 560 to 1800 mg/dL, 5.6 to 18 g/L
3. IgM: 50 to 300 mg mg/dL, 0.5 to 3 g/L
Abnormal IgA results:
1. Increased levels of IgA: Chronic infections (especially involving the gastrointestinal tract), inflammatory bowel
disease, rheumatic fever.
2. Decreased levels of IgA: Agammaglobulinemia, hypogammaglobulinemia, protein-losing gastroenteropathy,
hereditary IgA deficiency, chemotherapy and/or immunotherapy.
Abnormal IgG results:
1. Increased levels of IgG: Chronic infections, hyperimmunization, IgG multiple myeloma, liver disease, rheumatoid
arthritis (and other connective tissue diseases), rheumatic fever.
2. Decreased levels of IgG: Agammaglobulinemia, hypogammaglobulinemia, amyloidosis, leukemia, preeclampsia,
chemotherapy and/or immunotherapy.
Abnormal IgM results:
1. Increased levels of IgM: Infectious mononucleosis, lymphosarcoma, Waldenstrom’s macroglobulinemia, MGUS,
rheumatoid arthritis (and other connective tissue diseases).
2. Decreased levels of IgM: Agammaglobulinemia, hypogammaglobulinemia, amyloidosis, leukemia, chemotherapy
and/or immunotherapy.
2. Electrophoresis
Serum protein electrophoresis (SPE, SPEP) is a laboratory technique that is very commonly used to evaluate patients with high
serum protein, such as WM and multiple myeloma. In certain instances, despite normal serum protein levels, an SPE is performed
nonetheless for such conditions as unexplained neurological disorders and other diseases.
The basic SPE separates serum proteins based on their physical properties: the net charge (positive or negative) of the protein
molecules, and the size and shape of the proteins. There exist additional specialized SPE tests used on occasion when warranted:
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example includes zone electrophoresis and immunofluorescence / immunofixation SPE.
The resultant pattern of a typical SPE depends on the concentration of the two major types of serum proteins: albumin and globulins.
Albumin, produced by the liver, is the major protein constituent in normal serum. Globulins, on the other hand, usually represent
a much smaller fraction of serum proteins. The identification of subsets of globulins and the determination of their relative quantity
are the primary objective of SPE.
Albumin, the largest component of normal serum proteins, is also correspondingly the largest peak on the electrophoretic pattern,
and lies closest to the positive electrode. The next five protein components represent the globulin subsets: alpha 1, alpha2, beta1, beta2,
and gamma. The globulin peaks likes towards the negative electrode, with the gamma fraction closest to the negative electrode. Figure 1
shows a typical SPE pattern.
Components of Serum Proteins in SPE
Albumin, usually the largest peak, comprises approximately 60% of the total serum proteins. It is responsible for much of the
plasma’s colloidal osmotic pressure and serves as the major transport protein for large molecules such as fatty acids, bilirubin, many
drugs, and certain hormones.
Table 1. Indications for Serum Protein Electrophoresis.
• Suspected multiple myeloma, Waldenstrom’s macroglobulinemia, primary amyloidosis, or related disorder
• Unexplained peripheral neuropathy (not attributed to longstanding diabetes
mellitus, toxin exposure, chemotherapy, etc).
• New-onset anemia associated with renal failure / insufficiency and bone pain.
• Back pain in which multiple myeloma is suspected.
• Hypercalcemia, weight loss, fatigue, bone pain, abnormal bleeding.
• Rouleaux formations noted on peripheral blood smear.
• Renal insufficiency with associated serum protein elevation.
• Unexplained pathologic fracture or lytic lesion identified on X-ray.
• Bence Jones proteinuria.
The alpha1 globulin fraction includes alpha1-antitrypsin, thyroid- binding globulin, and transcortin. The alpha2 globulins are composed of
ceruloplasmin, alpha2-macroglobulin, and haptoglobin.
The beta1 globulin fraction is composed mostly of transferrin, and beta2 contains beta-lipoproteins. Rarely, IgA, IgM, and sometimes IgG,
along with complement proteins, can be identified in the beta fraction.
The gamma globulin fraction is of particular interest to WM patients and their physicians as immunoglobulins migrate to this
region of the electrophoretic pattern. Although immunoglobulins can be found throughout the entire electrophoretic spectrum, IgM
is typically well represented in the gamma region. The inflammatory marker C-reactive protein (CRP) is located in the area between the
beta and gamma fractions.
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Albumin
1
2
Alpha1
Alpha2
Beta
Gamma
Figure 1. Typical normal serum protein electrophoresis pattern.
Interpretation of SPE Results
The levels of serum proteins vary in response to physiologic changes in the body secondary to acute inflammation, malignancy,
traumatic injury, necrosis of tissues, burns, and chemical injuries.
As previously stated, the interpretation of SPE is primarily focused on the gamma region, which contains predominantlythe
immunoglobulins. Although many conditions can cause an increase in the gamma region, several disease states can cause a
homogenous spike-like peak. Monoclonal gammopathies, such as WM, MGUS, and multiple myeloma constitute a group of diseases
that are characterized by proliferation of a single clone of immature B-cells or plasma cells that produce a homogeneous M protein. The
characteristic M-spike is a classic feature on SPE.
Monoclonal and Polyclonal Gammopathies
Monoclonal gammopathies are characteristic of a clonal process that is malignant or potentially malignant. Polyclonal gammopathies on
the other hand may be the result of any number of reactive or inflammatory processes such as infections, connective tissue diseases, liver
diseases, malignancies, hematologic and lymphoproliferative disorders, and other inflammatory conditions.
An M protein (monoclonal protein) is characterized by the presence of a sharp, well-defined band with a single heavy chain and a
similar band with a kappa or lambda light chain. A polyclonal gammopathy is characterized by a broad diffuse band with one or
more heavy chains and kappa and lambda light chains.
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Table 2. SPE Protein Patterns and Associated Conditions or Disorders.
Increased albumin
Increased beta1 or beta2 globulins
Dehydration
Biliary cirrhosis
Carcinoma
Decreased albumin
Cushing’s disease
Chronic cachectic or wasting disease
Diabetes mellitus
Chronic infections
Hypothyroidism
Hemorrhage, burns, or protein-losing enteropathies
Iron deficiency anemia
Impaired liver function resulting from decreased synthesis
Malignant hypertension
of albumin
Nephrosis
Malnutrition
Polyarteritis nodosa
Nephrotic syndrome
Obstructive jaundice
Pregnancy
Third-trimester pregnancy
Increased alpha1 globulins
Pregnancy
Decreased beta1 or beta2 globulins
Protein malnutrition
Decreased alpha1 globulins
Alpha1-antitrypsin deficiency
Increased gamma globulins
Amyloidosis
Chronic infections
Chronic lymphocytic leukemia
Cirrhosis
Hodgkin’s disease Lymphoma
Rheumatoid and collagen diseases (connective
disorders)
Waldenstrom’s macroglobulinemia
Increased alpha2 globulins
Adrenal insufficiency
Adrenocorticosteroid therapy
Advanced diabetes mellitus
Nephrotic syndrome
Decreased alpha2 globulins
Malnutrition
Megaloblastic anemia
Protein-losing enteropathies
Severe liver disease
Wilson’s disease
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Decreased gamma globulins
Agammaglobulinemia
Hypogammaglobulinemia
13
tissue
Once an SPE has determined the presence of a monoclonal protein band (M-spike), the type of gammopathy needs to be identified by
further tests such as bone marrow biopsy, 24 hour urine collection for protein, flow cytometry, etc. The most common causes of
monoclonal gammopathy are multiple myeloma, Waldenstrom’s macroglobulinemia, solitary plasmacytoma, smoldering
multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukemia, heavy chain disease, and
amyloidosis. It is important to note than in some patients, the SPE may appear normal because the complete monoclonal
immunoglobulin is absent or is present at a very low level.
Albumin
1
2
Gamma
Alpha1
Alpha2
Beta
Figure 2. Abnormal SPE in a patient with WM.
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OTHER IMPORTANT TESTS FOR WALDENSTROM’S PATIENTS WITH RELATED INFORMATION
URINE TESTS
Bence-Jones proteins: Abnormal two-unit (dimers) complexes of immunoglobulin light chains found in the urine of some patients,
particularly those with multiple myeloma, and Waldenstrom’s macroglobulinemia.
pH (urine): Urinary pH has a wider range than blood pH because the kidneys have a major role in maintaining the pH in the
circulation close to neutral (pH 7.35-7.45). If the pH in the blood falls and becomes more acid, the kidneys increase the excretion of
hydrogen ions (acids). If the pH in the blood rises and becomes more alkaline, the kidneys increase the excretion of bicarbonate
ions (alkalines).
Protein (urine): Normal urine contains little significant protein. An increase in normal protein or simply protein in the urine
(proteinuria) is usually caused by kidney disease. An increase in abnormal proteins (monoclonal proteins) is usually caused by
neoplasms (multiple myeloma or lymphomas).
Uric acid: A small breakdown product of purines, which are part of DNA. Uric acid is excreted primarily by the kidneys, as well as by
the gastrointestinal tract. Increased uric acid crystals are deposited in various tissues: knee, elbow, ankle and particularly the “big
toe”
joint are favored areas. “Gout” is the general term used for the inflammatory and very painful condition caused by uric acid crystal
deposition in joints. Uric acid increases with rapid cell turnover, such as cancer (particularly during chemotherapy for cancer where
there is large amount of cell death), and also as a result of drug therapy (diuretics in particular), and in many other conditions.
Urinalysis: A low-cost test in which a urine specimen is examined in order to screen for various diseases. Routine urinalysis is used to
detect renal disease (e.g. glomerulonephritis), urinary tract disease, or metabolic disease like diabetes mellitus.
BONE MARROW BIOPSY
Biopsy: A general term referring e i t h e r to the surgical procedure in which a small piece of tissue is removed from a patient or the tissue
itself. The changes present in the tissue are interpreted by a pathologist, who renders a diagnosis based on relatively standardized
criteria. Biopsies are used to diagnose a disease; determine the extent of a disease (e.g. metastasis in cancer); and determine the
adequacy of surgical removal.
Bone marrow aspiration and biopsy: Bone marrow is the soft tissue found in the middle of certain bones (hip and pelvis,
sternum, spinal vertebrae, amongst others) and is the site where red blood cells, white blood cells, and platelets are produced.
Bone marrow aspiration and biopsy is obtained when there is a need to explain an abnormal finding relating to an individual’s red
blood cell, white blood cell, or platelet count. This procedure can also performed when a physician wishes to assess the statusof a
known hematological disease; determine if treatment is required; determine if a treatment for a known disorder requires further
modification; or to simply assess the result of a particular treatment (e.g. after chemotherapy). The procedure is either performed
in a physician’s office with local anesthesia, or can be performed in a more monitored setting under light sedation. Bone marrow
biopsies are usually obtained from the posterosuperior iliac spine (posterior upper aspect of the hip bone). The skin is cleaned with an
antiseptic solution, and the area is anesthetized using local anesthetic. A large-bore needle is inserted, and for the aspiration a fluid
specimen in which bone marrow is suspended is removed. For a biopsy specimen, a solid core of marrow cells accompanied by bone is
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removed. The resulting specimens are evaluated by a pathologist, and a diagnosis is rendered thereafter. Specialized tests can be
performed, such as flow cytometry, with the aspiration and biopsy specimens. Discomfort from the procedure varies among patients;
most individuals will note deep aching bone pain during the procedure and for a few days afterwards – hence the popularity of having
the procedure done under light sedation if available.
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TESTS FOR SELECTED CONDITIONS IN WALDENSTROM’S MACROGLOBULINEMIA
AMYLOIDOSIS
A group of conditions of diverse etiologies characterized by the accumulation of insoluble fibrillar proteins (amyloid) in various
organs and tissues of the body such that vital function is compromised. The associated disease states may be inflammatory,
hereditary, or neoplastic, and the deposition can be local or generalized or systemic. Amyloidosis in Waldenstrom’s
macroglobulinemia is usually caused by fragments of light chains and affects predominantly the kidneys and heart.
Many tests may be used to diagnose amyloidosis and determine which parts of the body are affected. A biopsy is the only way to
make a definitive diagnosis of amyloidosis. Secondary amyloidosis is usually diagnosed from a biopsy of a small amount of tissue,
usually abdominal fat, for examination under a microscope. An alternative method is a fine needle aspiration biopsy (FNAB) from
subcutaneous fat. Imaging tests may be used to find out whether organs such as the heart or kidneys are affected. Biopsies may also
be taken from the liver, nerves, heart or kidneys. These are more invasive procedures and may require hospitalization.
Nerve biopsy is used to evaluate primary or secondary neuropathies or systemic diseases like amyloidosis. Various special studies can be
done on a properly obtained nerve biopsy, including biochemical analysis, electron microscopy, histology, immunochemistry, various
molecular studies, and virology. The site selected for the nervebiopsy is critical and should come from an area of active disease.
The sural nerve at the lower part of the leg is the preferred site for the peripheral neuropathy associated with Waldenstrom’s
macroglobulinemia.
Direct fluorescent antibody method: A technique in which a molecule of interest is detected directly, using an antibody labeled or tagged
with a fluorescent molecule. This test is often used to detect the presence of immune complex depositions in tissues such as the kidneys. It is
used often in the histological diagnosis of amyloidosis.
ANEMIA
Anemia refers to a deficiency of red blood cells and/or hemoglobin. This results in a reduced ability of blood to transfer oxygen to the
tissues, causing hypoxia; since all human cells depend on oxygen for survival, varying degrees of anemia can have a wide range of
clinical consequences. Hemoglobin, the oxygen-carrying protein in the red blood cells has to be present to ensure adequate
oxygenation of all body tissues and organs.
The three main classes of anemia include excessive blood loss (acutely such as a hemorrhage or chronically through low-volume loss),
excessive blood cell destruction (hemolysis) or deficient red blood cell production (ineffective hematopoiesis).
Anemia is the most common disorder of the blood. There are several kinds of anemia, produced by a variety of underlying
causes. Anemia can be classified in a variety of ways, based on the morphology of RBCs, underlying etiologic mechanisms, and
discernible clinical spectra, to mention a few.
Iron (iron-binding capacity, total iron-binding capacity, TIBC): Iron is an essential mineral that is bound to hemoglobin and
responsible for the transportation of oxygen. The term “total iron” is the amount of iron actually present in the serum. In contrast,
the term “total iron-binding capacity” indicates the amount of iron that could be present in the circulation (i.e. be bound by
the existing carrier proteins in the serum) and is a chemical approximation of the amount of transferrin (the protein responsible for
the transportation of iron in the blood). There are now direct measurements of transferrin available but they are not widely used.
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Iron and TIBC are often part of a general chemistry panel which can be performed on highly automated instruments.
Pyruvate kinase: An enzyme that participates in the anaerobic metabolism of glucose. Its absence is the most common cause of
congenital hemolytic anemia. It is measured in the evaluation of chronic hemolytic anemias. A decrease in pyruvate kinase is noted in
hemolytic anemias, acute leukemias, and aplastic anemia.
Transferrin: A protein that is a carrier of iron in the circulation. Transferrin levels correspond to the maximum amount of iron that
can be bound to the protein, a value that is designated “total iron- binding capacity” (TIBC). Transferrin levels may be requested in the
presence of suspected iron-deficiency anemia, or in those with chronic liver disease, renal failure, malnutrition, lead poisoning, and
other conditions. Transferrin levels are increased in severe iron deficiency anemia, and may be decreased in severe illnesses such as liver
disease, cancer, iron overload, and severe malnutrition.
COLD AGGLUTININ DISEASE
Cold agglutinin disease is an autoimmune hemolytic anemia caused by autoantibodies that bind to red blood cells at temperatures
reached in the capillaries of the skin and subcuntaneous tissues, causing red blood cell destruction (hemolysis). The IgM antibodies are
monoclonal in origin, having either kappa or lambda light chains but not both, and are seen in certain patients with Waldenstrom’s
macroglobulinemia.
Cold agglutinins are antibodies that cause red blood cell clumping at low temperatures. They are detectable in low levels in normal
patients, increase after certain infections, and are insignificant if they don’t destroy red blood cells. Cold agglutinins are used to
help diagnose certain types of atypical pneumonias and certain hemolytic anemias.
CRYOGLOBULINEMIA
Cryoglobulins are abnormal proteins detected in the laboratory by chilling serum to 32˚C. Patients with cryoglobulinemia (affects
certain WM patients) experience pain, cyanosis, and numbing of fingers and toes when exposed to cold. The serum specimen drawn
from the patient needs to be kept warm until testing.
Clinical disease is characterized by cryoglobulins in the serum; often associated with immune complex antigen-antibody
(cryoprecipitable immunocomplex) deposits in the kidneysand other tissues. Three types of cryoglobulinemia have been
described: Type I (monoclonal cryoglobulinemia); Type II (mixed cryoglobulinemia) was first noted in WM, and can be seen as well in
auto-immune disorders; Type III (mixed polyclonal-polyclonal cryoglobulinemia) can be seen with auto-immune diseases, infections,
and other medical diseases.
PERIPHERAL NEUROPATHY
A clinical symptom where there is a permanent or transient problem with the functioning of the nerves outside the spinal cord. The
symptoms of a neuropathy may include numbness, weakness, burning pain, and loss of reflexes. The pain may be mild or severe and
disabling.
Electromyography (EMG): Electromyography measures minute electrical discharges produced in skeletal muscle both at rest and
during voluntary contraction and is used in the diagnosis of neuromuscular disease. The electrode for EMG is inserted through the
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skin, and the resulting electrical discharge or motor unit potential is recorded. Nerve conduction studies, which constitute a
separate diagnostic protocol, can be performed simultaneously. Nerve conduction studies measure the speed at which nerves carry
electrical signals and are often used to diagnosed peripheral neuropathy, as well as carpal tunnel syndrome.
Nerve biopsy: A biopsy used to evaluate primary or secondary neuropathies or systemic diseases like amyloidosis. Various special
studies can be done on a properly obtained nerve biopsy, including biochemical analysis, electron microscopy, histology,
immunochemistry, various molecular studies, and virology. Thesite selected for the nerve biopsy is critical and should come from an
area of active disease. The sural nerve at the lower part of the leg is the preferred site for the peripheral neuropathy associated with
Waldenstrom’s macroglobulinemia.
Nerve conduction study: A noninvasive method for assessing a nerve’s ability to carry a neural impulse and its speed of transmission. In
these studies, larger peripheral motor and sensory nerves are electrically stimulated at various intervals along a motor nerve.
Typically, two metal plates are placed on the skin at a distance from each other. An electrical stimulus passes through one plate
and causes the nerve to fire, resulting in a “compound” muscle action potential that can be measured and recorded.
VISUAL DISORDERS
Fluorescein angiography: A technique used to diagnose chorioretinal disease based on the enhancement of anatomic and
vascular details in the retina after intravenous injection of fluorescein. The distribution pattern of the fluorescein dye can be viewed
and photographed with a fundus camera as a function of its intrinsic fluorescence.
Fundoscopy (Fundoscopic Examination, Ophthalmoscopy): The examination of the back of the eye (fundus) with an
ophthalmoscope, which is part of the routine examination of a patient. Ophthalmoscopy allows a magnified evaluation of the blood
vessels, nerves, and retina. Retinal hemorrhages, retinal detachments, swollen blood vessels, as is the case in patients with elevated
serum viscosity and other abnormalities, can be easily viewed using this technique.
Tonometry: A technique that measures intraocular pressure (in mm Hg) by contact (indentation of or applanation on) or noncontact
(by a puff of air) on the eyeball. Tonometry is used to diagnose and manage glaucoma and ocular hypertension, and in routine ocular
examination. Normal intraocular pressure ranges from 15 to 20 mm Hg.
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APPENDIX 1: GLOSSARYOF MEDICAL TERMS RELATING TO TESTS
NOTE: This Glossary is meant to assist patients in understanding some of the targets for medical testing. Not all patients will have all
tests mentioned in this booklet. A broader list of medical definitions for the Waldenstrom patient can be found in the
“Comprehensive Glossary: Medical Terms for the Waldenstrom Patient,” a recent IWMF publication.
The U.S. National Institutes of Health’s National Cancer Institute maintains an expansive on-line dictionary of cancer terms at
www.cancer.gov/dictionary
Acid phosphatase: Group of enzymes present in the prostate, semen, liver, spleen, red blood cells, bone marrow, and platelets that
can be separated and analyzed according to their sources. Increased in prostate cancer, prostate infection, bone disease, multiple
myeloma.
Acute phase reactants (APRs): APRs are increased in acute and chronic inflammation, tuberculosis, diseases characterized by elevated
paraproteins (e.g. WM and multiple myeloma), and rheumatoid arthritis. Decreased in hyperviscosity.
Alanine aminotransferase (ALT or SGPT): Enzyme found primarily in the liver, with lesser amounts noted in the kidneys, heart, and
muscles. Used as early indicator of liver damage. Increased in liver disease.
Albumin: The most abundant protein found in the blood circulation, albumin is needed to maintain the osmotic pressure within
blood vessels, without which fluids would leak out of the circulation. Albumin provides nutrition to tissues and binds various
molecules, such as hormones, vitamins, drugs, and enzymes, transporting them through the body. Albumin is synthesized in the liver
and is extremely sensitive to liver damage. Increased in dehydration; decreased in liver disease, chronic disease, cancer, malnutrition,
thyroid disease, burns, heart failure, and kidney disease.
Alkaline phosphatase (ALP or Alk Phos): Enzyme normally present in the blood. Various subtypes (isoenzymes) are found in the liver,
intestine, and bone cells. Alk phos levels are increased in diseases affecting the bone and/or liver.
Ammonia: Ammonia is produced in the liver, intestine, and kidneys at the end product of protein metabolism. The liver converts
ammonia into urea, which is then excreted by the kidneys. Ammonia is increased in liver disease, severe congestive heart failure,
gastrointestinal hemorrhage, and certain severe hemolytic diseases (e.g. hemolytic disease of the newborn).
Amylase: Enzyme synthesized in the pancreas and secreted into the gastrointestinal tract, which helps digest starch and glycogen in
the mouth, stomach, and intestine. Elevated in acute pancreas diseases or acute salivary gland disease, may be increased or
decreased in pancreatic cancer, decreased in chronic pancreatic disease, hepatitis.
Anti-double stranded DNA antibodies (anti-ds DNA antibodies): Autoantibody that is directed against DNA and commonly seen in
systemic lupus erythematosus. Anti-ds DNA antibodies are usually measured as part of a battery of antibodies in a work-up of a patient
with known antinuclear antibodies.
Antinuclear antibodies (ANA): A group of circulating antibodies, commonly seen in connective tissue diseases/autoimmune
diseases that are directed against various antigens in the nucleus including histones, double- and s ingle stranded DNA, and
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ribonucleoprotein. Although the antibodies are not themselves harmful, they sometimes form antigen-antibody complexes that
cause tissue damage.
Anti-neutrophil cytoplasmic antibody (ANCA): Autoantibodies with various specificities against myeloid-specific lysosomal enzymes.
Most often seen in certain forms of vasculitis, connective tissue diseases, unexplained renal failure, drug-induced reactions.
Anti-tetanus toxoid antibodies: Measurement of antibodies to tetanus toxoid is used to assess the status of tetanus immunity. IgM
antibodies are increased following acute exposure and the IgG antibodies are present in individuals who have adequate serum levels of
anti-tetanus antibodies. The antibodies are present in immunized individuals; absent in individuals susceptible to tetanus.
aPTT (activated partial thromboplastin time): also known as PTT (partial thromboplastin time); used in preoperative screening for
increased bleeding tendencies and to monitor therapy with heparin and other forms of anticoagulation therapy. The PTT test evaluates
the time required for the clotting proteins or coagulation factors to form a fibrin clot. The test is noted to be elevated in coagulation
factor deficiencies, Hodgkin’s disease, leukemia, liver disease, von Willebrand’s disease, drugs.
Arterial blood gas: Blood gases are used to assess pulmonary function, acid-base levels of the blood, and to monitor respiratory therapy.
Whole blood is drawn from an artery, usually at the radial artery at the wrist.
Aspartate aminotransferase (AST or SGOT): Enzyme found primarily in the liver; released into the bloodstream in liver disease, heart
attacks, renal disease and skeletal muscle disease.
Bence-Jones proteins: Abnormal two-unit (dimers) complexes of immunoglobulin light chains found in the urine of some patients,
particularly those with multiple myeloma and Waldenstrom’s macroglobulinemia.
Beta-2-microglobulin: Cell membrane associated protein (part of the class I MHC molecule) that is specifically elevated in inflammation,
renal disease, AIDS, and in some cancers, including WM, CLL, and multiple myeloma. Urine levels of beta-2-microglobulin can be
affected by kidney disease.
Bilirubin: Bilirubin is a metabolized product of hemoglobin when red blood cells break down at the end of their usual 120 day lifespan.
Bilirubin joins the bile fluid and is transported from the liver to the gallbladder to the intestines. Most is normally eliminated by the
bowels. Increased production or decreased excretion of bilirubin can cause a yellowing (jaundice) of the skin and the whites of the
eyes and a darkening of the urine. Bilirubin is increased in liver disease, hemolytic diseases, and obstruction of normal bile flow.
BUN (blood urea nitrogen): Nitrogen in the form of urea is the major waste product of protein metabolism and is excreted through
the kidneys. BUN is measured in serum, plasma, and urine, and is most often measured in conjunction with creatinine as an
indicator of kidney function. Increased BUN usually reflects kidney disease or unusually high protein catabolism. Decreased BUN is
noted in malnutrition, severe liver disease, and in pregnancy.
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Calcium: The mineral calcium is located in large quantities predominantly in the bones and teeth. Not only is calcium
important to the structure of bone, it is also critically important to many metabolic processes in the body such as muscle contraction,
transmission of nerve signals, blood clotting, and inhibition of cell destruction. Blood tests indicating elevated calcium levels may occur
in parathyroid disease and tumors, bone disease, multiple myeloma, metastatic cancer, kidney disease, adrenal insufficiency, and
excessive use of antacids. Decreased levels are seen in low functioning parathyroid glands, malabsorption, kidney failure, and Cushing’s
disease.
Chemistry profile / metabolic profile: A generic term referring to a battery of tests measuring substances in the blood that may be
altered in common diseases. Often included in the profile are albumin, BUN, calcium, cholesterol, creatinine, glucose, alkaline
phosphatase, lactate dehydrogenase, phosphorous, ALT, AST, and electrolytes.
Chloride: Chloride is the major negative electrolyte (anion) in the extracellular fluid and interacts with sodium to maintain the
osmotic pressure of blood, thereby regulating blood volume and arterial pressure.
Cholesterol: A blood lipid (fat) that is a normal component of red blood cells and is an important constituent of cell membranes. It
is absorbed from the diet, synthesized by the liver, and used by the body for fat digestion and is a chemical parent molecule for
hormones synthesized by the adrenal glands, ovaries, and testes. Because increased cholesterol levels (and very low levels of HDL
cholesterol) have been associated with atherosclerosis, coronary artery disease, and an increased risk of death due to heart attacks
and strokes, cholesterol is commonly measured and included in most routine chemistry panels. Cholesterol attached to highdensity lipoprotein (HDL cholesterol) is metabolized in an optimal fashion and is known as the “good” cholesterol. Cholesterol
attached to low-density lipoprotein (LDL cholesterol) and to very low-density lipoprotein (VLDL) is known as “bad” cholesterol. Most
cholesterol tests now measure total, HDL, LDL and VLDL cholesterol. For optimum results the patient should fast for 12 hours
before the test.
Coagulation panel/studies: A group of assays designed to efficiently identify a cause of hemorrhage in a bleeding patient. The assays
include prothrombin time (PT), activated partial thromboplastin time (aPTT), platelet count, and bleeding time.
Cold agglutinin: Cold agglutinins are antibodies that cause red blood cell clumping at low temperatures. They are detectable in low
levels in normal patients, increase after certain infections, and are insignificant if they don’t destroy red blood cells. Cold agglutinins
are used to help diagnose certain types of atypical pneumonias and certain hemolytic anemias.
Complement: Complement is a complex of more than 25 proteins present in the serum that mediate a nonspecific inflammatory
response to various antigens through an enzyme reaction sequence. Complement results in a number of biologically active products
implicated in certain immune disorders. Complement proteins are designated as C1 through C9, only several of which are routinely
measured. Deficiencies in complement are usually noted infections and autoimmune diseases.
Complement fixation test: A widely used test method which depends on the ability of complement to interact with antigen-antibody
(Ag-Ab) complexes. Complement fixation tests can be used to detect Ag-Ab complexes, soluble and particulate Ags, Abs, bacteria, fungi,
and immunoglobulins.
Complete blood c ount (CBC): The CBC is a commonly ordered test which measures cells in the circulation and hemoglobin by
automated instruments. The CBC measures hematocrit, hemoglobin, the volume (MCV) of each red blood cell (RBC), hemoglobin
per RBC (MCH), concentration of hemoglobin in the red blood cell (MCHC), number of RBCs, white blood cells (WBCs), and
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platelets; a differential count or “diff ” counts the lymphocytes, monocytes, eosinophils, basophils, and neutrophils. If the automated
differential is abnormal, a manual differential is performed to verify the results. The manual differential is labor intensive and
involves the preparation of a microscope slide and visually counting the cells under a microscope.
CBC reference range (adult):
RBCs
Male
Female
MCV
MCH
MCHC
Hematocrit
Male
Female
Hemoglobin
Male
Female
WBCs
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Platelets
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4.5-5.4 x 1012//L
3.6-5.0 x 1012/L
80-100 fL
26-32 pg
30%-60%
42%-54%
38%-46%
14-18 g/dL
12-16 g/dL
4,000-10,000/mm3
48%-77%
16%-43%
0.6%-9.6%
0.3%-7%
0.3%-2%
130-400,000/mm3
23
CBC abnormal values:
Decreased in:
Increased in:
WBC
viral infection
bacterial infection, leukemia
Hematocrit
anemia hemodilution
polycythemia
hemoconcentration in blood loss
Hemoglobin
anemia hemorrhage fluid retention
hemoconcentration in polycythemia,
dehydration
RBCs
anemia fluid overload
polycythemia dehydration, hemorrhage
MCV
iron deficiency anemia
genetic DNA disorder
macrocytic anemia (B12 def )
thalassemia alcohol excess
MCH
microcytic anemia iron deficiency
macrocytic anemia (B12 def )
alcohol excess
MCHC
iron deficiency anemia
spherocytosis
Neutrophils
radiation or chemo, infections (viral
or overwhelming bacterial
infections), hypersplenism, collagen
vascular diseases, vitamin deficiency,
folic acid deficiency
infections, heart attacks, stress, metabolic
diseases, inflammation
Eosinophils
stress, Cushing’s syndrome
(excess of adrenal steroids)
allergy, parasitic infections, skin disorders,
cancer, collagen vascular disease
Basophils
hyperthyroidism, ovulation,
pregnancy, stress
chronic myelocytic leukemia, polycythemia
vera, Hodgkin’s disease, certain types of
anemias
Lymphocytes
chronic debilitating illness,
immunodeficiency
infections, lymphocytic leukemia, certain
immune diseases, ulcerative colitis
Monocytes
infections, collagen vascular disease, cancer,
leukemias and lymphomas
C-reactive protein (CRP): A protein produced in the liver, CRP is part of the “acute phase reactants” whose levels in the serum rise quickly
during inflammation or acute physiologic stress. Functions include complement activation, binding of T-cells, inhibition of blood clot
retraction, suppression of platelet and lymphocyte function, and enhancement of phagocytosis by neutrophils. CRP is a biological
marker for acute injury and is often measured with the erythrocyte sedimentation rate (ESR, Sed Rate), another nonspecific marker of
inflammation.
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Creatine phosphokinase (CK, CPK): An enzyme found primarily in the heart and skeletal muscle and in low concentration in the
brain. Levels are elevated when there is injury to skeletal muscle, to the heart muscle (heart attack), or stroke (brain attack).
Creatinine: Creatinine is the end product of creatine metabolism, which is excreted by the kidney and is used to diagnose and
monitor kidney disease. Creatinine may be measure in urine and in serum (blood).
Creatinine clearance: This test reflects the body’s ability to excrete creatinine and is used to diagnose and determine kidney function.
A 24 hour urine collection and a serum sample are required.
Cryoglobulins: Cryoglobulins are abnormal proteins detected in the laboratory by chilling serum to 32˚C. Patients with
cryoglobulinemia (affects certain WM patients) experience pain, cyanosis, and numbing of fingers and toes when exposed to cold.
The serum specimen drawn from the patient needs to be kept warm until testing.
Cryptococcosis: A fungal infection caused by Cryptococcus neoformans that can occur in blood, lungs, spinal fluid, and other body sites.
Serum and occasionally cerebrospinal fluid are tested.
Cryptosporidia: An intestinal and respiratory tract parasite which, in humans, causes severe chronic diarrhea in patients with AIDS and
decreased immunoglobulins. The infection is mild in individuals of normal immunity.
Cytomegalovirus (CMV): A member of the herpesvirus g roup which is global in distribution. It is transmitted by blood and is rarely
a serious infection, but has been linked to chronic fatigue syndrome. In immunocompromised patients (AIDS, bone marrow
transplantation), CMV infection can be serious. CMV testing in adults is based on measuring antibody levels in serum. CMV
infections are very serious in pregnancy, as birth defects can be the result.
Direct antiglobulin test (direct Coombs test): A test used to detect antibodies attached to the RBCs caused by antibodies, complement
components, or both. The test identifies an antigen-antibody reaction but does not specify the antibody responsible for the
reaction. Autommune hemolytic anemia (rupture of the red blood cells caused by an immune reaction) may be linked to various
drugs, hemolytic transfusion reaction, and hemolytic disease of the newborn. A positive result helps differentiate autoimmune and
secondary immune hemolytic anemia, which may be associated with an underlying disease such as lymphoma or drug-induced.
Direct and indirect Coombs tests are performed together.
Direct fluorescent antibody method: A technique in which a molecule of interest is detected directly, using an antibody labeled or
tagged with a fluorescent molecule. This test is often used to detect the presence of immune complex depositions in tissues such
as kidneys. It is used often in the histological diagnosis of amyloidosis.
Epstein-Barr virus (EBV): EBV belongs to the herpesvirus family and is the DNA virus believed to cause infectious mononucleosis. EBV
is associated with Burkitt’s lymphoma, nasopharyngeal carcinoma (very high incidence in China), and lymphoma in
immunocompromised patients, including AIDS patients. Several serologic markers are used to diagnose EBV infections and determine the
stage of infections (EBV IgM and EBV IgG).
Erythrocyte sedimentation rate (ESR, Sed Rate): The ESR is a simple laboratory test that measures the rate at which red blood cells
in well-mixed venous blood settle to the bottom of a special test tube. This serves as a nonspecific indicator of inflammation and
should be performed within a few hours (12) of obtaining the blood specimen. Although it is routinely ordered by many
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physicians, it is nonspecific, and inflammation is better monitored by serial measurement of C-reactive protein. Note that anemia and
paraproteinemia (such as is often the case in WM) almost always invalidate the results.
Erythropoietin: Erythropoietin is a hormone produced by the kidneys that stimulates red blood cell production. It plays an important role
in regulating oxygen metabolism and is severely decreased in end- stage renal disease. A simple blood test can determine the level of
erythropoietin in a patient; some patients develop erythropoietin antibodies, and these can be measured as well. Procrit is synthetic
erythropoietin produced by recombinant DNA technology.
Febrile agglutinins: Febrile agglutinins tests identify agglutinins in the serum causing fever due to suspected bacterial infection. Bacterial
antigens often associated with febrile agglutinins are brucellosis, salmonellosis, typhoid fever, and tularemia (very dangerous
infections for the immunocompromised patient).
Ferritin: Ferritin is the major iron storage protein which is normally present in small amounts in serum. In healthy adults, serum ferritin
levels are directly related to the amount of iron stored in the body. Ferritin is 23% iron by weight and, while it is usually measured
with iron and iron-binding studies, it is the most accurate single test for iron deficiency.
Folic acid: Folic acid is a water-soluble vitamin that can’t be synthesized by mammals. Folic acid is a part of normal diet and is present in
raw fruits and vegetables, kidney, and liver, and can be destroyed by extensive cooking. Folic acid deficiency, like that of vitamin B12,
causes megaloblastic anemia, which is characterized by low numbers of enlarged RBCs.
Glucose: Glucose is the principal sugar in the body, the metabolism of which provides most of the body’s energy. Excess glucose or
hyperglycemia is a central feature of diabetes mellitus and can cause irreversible damage to blood vessels, the eyes, kidneys and
other tissues. Decreased glucose or hypoglycemia, exceedingly rare in individuals (apart from diabetics on medication), can cause
metabolic shutdown due to lack of energy. An elevated glucose level warrants further investigation, particularly a glucose tolerance
test.
Haptoglobin: A protein in the circulation that is an acute phase reactant; its level in the serum increases in response to acute
inflammation or infection, stress, or necrosis (death of tissue). Its major role is to bind hemoglobin released from RBCs that undergo
natural cell death, preventing the accumulation of hemoglobin in the plasma. After the iron has been removed and “recycled” in the
body, the haptoglobin-bound hemoglobin is eliminated by the reticuloendothelial monocyte-phagocytic system.
HDL-cholesterol: The cholesterol that is bound to high-density lipoprotein. Increased HDL-C and HDL-C / total cholesterol ratios are
associated with increased longevity and decreased morbidity and mortality from heart attacks, strokes, and other vascular diseases.
Patients should fast for 12 hours prior to drawing the specimen.
HDL / LDL ratio: The ratio of cholesterol carried by high-density lipoprotein to that carried by low-density lipoprotein, which allows
rapid risk stratification for atherosclerosis-related cardiac disease; the HDL/LDL ratio is decreased by saturated fatty acid.
Helicobacter pylori: A bacterium that has been linked to the development of gastric and duodenal ulcers, hypertrophic
gastropathy, gastric adenocarcinoma, and non-Hodgkin’s lymphoma of the stomach. It is present in 10-50% of healthy young
persons and up to 60% of those 60 years or older. 90% of patients with stomach cancer have been infected by H. pylori. H. pylori
may be spread by intrafamilial contacts. A simple stool test or stomach biopsy ca n detect infection. Treatment is usually with a two-week
oral course of triple-antibiotic therapy.
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Helper T-cell/suppressor ratio: The ratio of CD4 helper T-cells (T-lymphocytes) to CD8 suppressor T-cells is normally 1.5-2.0. In
AIDS this ratio is the single best monitor of the patient’s clinical status, where less than 0.5 is commonly seen, and values of 0.1 or less
predict fulminant clinical deterioration. In immunocompromised individuals, such as Waldenstrom’s patients or post-transplant
patients, the CD4/CD8 ratio is used as well to assess immune status. The helper to suppressor ratio is most commonly determined by
flow cytometry.
Hematocrit (Hct): Hematocrit is the percentage of whole blood that corresponds to red blood cells (erythrocytes). There are two basic
methods for this determination. The automated method is more commonly performed and is a calculated hematocrit rather than a
direct measurement. It is determined by the formula MCV (mean corpuscular volume) x red blood cell number, where MCV is the
average volume of red blood cells. See Complete blood count (CBC).
Hemoglobin (Hgb): Hemoglobin is a protein that is the major constituent of red blood cells. The primary role of hemoglobin is to
transport oxygen as well as buffer the carbon dioxide produced by respiration. There are several forms of hemoglobin. Hemoglobin F is
formed in the fetus and is the major hemoglobin until birth. At birth, up to 30% of the hemoglobin is hemoglobin A. In adults,
hemoglobin is primarily hemoglobin A with small amounts of hemoglobin F and A2. Hemoglobin defects are inherited and termed
hemoglobinopathies. Altered hemoglobins often do not have the same oxygen-carrying capacity as hemoglobin A. In individuals with
partial defects (traits) of hemoglobin, hemoglobin exists in both the normal and altered state, and those with the trait often do not
exhibit overt symptoms. Hemoglobin variants are detected by hemoglobin electrophoresis.
High-density lipoprotein (HDL): A heterogeneous class of molecules found in the blood which includes proteins (33% by weight),
cholesterol (30%), phospholipids (29%), triglycerides (8%), cholesterol esters, and apolipoproteins. HDL is involved in the
transportation of cholesterol from the intestine. The larger the HDL molecule, the more efficient the lipid transportation and, by
extension, breakdown of lipids. HDL levels are the single most important predictor of coronary heart disease (CHD) given that several
risk factors for CHD (e.g. smoking, obesity, and lack of exercise) may lower HDL; HDL has an inverse relation with VLDL and LDL
(lipoproteins known to be atherogenic); and HDL may interfere with atherogenesis by promoting reverse cholesterol transport or
preventing aggregation of LDL particles in the arterial wall. Most physicians order a fasting blood test known as a lipid profile to
determine risk status; the tests measure total cholesterol, triglycerides, HDL, and LDL.
Immunoglobulins (antibodies): Immunoglobulins are highly specific molecules produced by the immune system’s B-lymphocytes in
response to a foreign substance (antigen). See immunoglobulins in glossary.
Iron (iron-binding capacity, total iron-binding capacity, TIBC): Iron is an essential mineral that is bound to hemoglobin and
responsible for the transportation of oxygen. The term “total iron” is the amount of iron actually present in the serum. In contrast,
the term “total iron-binding capacity” indicates the amount of iron that could be present in the circulation (i.e. be bound by
the existing carrier proteins in the serum) and is a chemical approximation of the amount of transferrin (the protein responsible for
the transportation of iron in the blood). There are now direct measurements of transferring available but they are not widely used.
Iron and TIBC are often part of a general chemistry panel which can be performed on highly automated instruments.
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Lactate dehydrogenase (LDH): Lactate dehydrogenase is an enzyme present in the cytoplasm of all cells; it catalyzes the interconversion
of lactate and pyruvate. Measurement of total LDH activity is used to screen for liver, muscle, and myocardial disease. LDH is often
used as well as a marker for certain leukemias, lymphomas, anemias, and multiple myeloma. LDH isosenzymes can be fractionated to
determine the predominant source of LDH. Isoenzymes are noted in the heart and red blood cells (LD1, LD2); platelets, lungs and
skeletal muscle (LD3); liver and skeletal muscle (LD4, LD5).
LDL-cholesterol: Cholesterol that is transported in the circulation by LDL (low density lipoprotein) which, when elevated, is a major risk
factor for atherosclerosis. See Low-density lipoprotein.
Low-density lipoprotein (LDL): Lipoproteins are proteins with bound lipids, of which cholesterol is the most important clinically.
LDL is in the beta group of lipoproteins, which has been linked to atherosclerosis and coronary artery disease. LDL- cholesterol is
measured by extracting the LDL-cholesterol from the other lipoprotein-cholesterol fractions (e.g. the alpha or high- density
lipoproteins or HDL). As part of a lipid profile whereby triglycerides, HDL, LDL and VLDL are measured, the patient is required to
undergo an overnight fast to obtain the most accurate specimen.
Lupus anticoagulant: A generic term for IgG or IgM class antibodies that arise spontaneously in patients with lupus erythematosus
(LE) and are directed against various components of coagulation factors. Lupus anticoagulants have also been reported in patients
with HIV, deep vein thrombosis, lymphomas, and others. Lupus anticoagulants include anticardiolipin and other antiphospholipid
antibodies.
Lyme disease: Lyme disease is caused by Borrelia burgdorferi, a bacterium that is transmitted to humans via the deer tick Ixodes
dammini. The disease responds to proper antibiotic therapy but can become chronic. Diagnosis is by clinical signs (there are three
different stages) and by serial serological measurement of IgG and IgM. Lyme disease has been suggested to be a causation factor in
a host of chronic diseases such as chronic fatigue syndrome, fibromyalgia, and even Waldenstrom’s macroglobulinemia – definitive
proof of association however remains elusive.
Magnesium (Mg++): An intracellular ion required for many metabolic processes that involve carbohydrates, proteins, and nuclear acids.
When magnesium is bound to the high-energy compound known as ATP, it acts as a cofactor in enzymatic reactions and is important in
neuromuscular activity.
MCH, MCHC, MCV: Red blood cell indices. See Co m pl e te bl o o d co unt (CBC).
Mycobacterium: The genus Mycobacterium contains many species of bacteria, the most well-known of which is M. tuberculosis,
which causes tuberculosis and continues to be the major cause of health problems throughout the world. Another Mycobacterium of
importance is M. leprae which causes leprosy. The other species of Mycobacterium were thought until recently to be relatively
benign. The use of chemotherapy and immunosuppressive drugs, and the appearance of AIDS have provided the other
Mycobacterium species with opportunities to cause severe infections in immunocompromised patients.
Myelin basic protein: A protein that is a major component of myelin.
In adults, an elevation of myelin basic protein in the serum occurs in multiple sclerosis and indicates active destruction of myelin.
Neutrophils: see Complete blood count (CBC).
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Osteoporosis screening: Bone undergoes a continuous cycle of formation (osteogenesis) and resorption (osteoclasis) that is collectively
termed remodeling. Substances known as biochemical marker are excreted in the urine and can be used clinically to determine
whether bone is being formed or resorbed. The substances excreted during bone resorption include hydroxyproline,
deoxypyridinoline, and the cross-linked N-ends of the protein collagen I (N-telopeptides) which appear to be the most specific
indicator of active bone resorption and evolving osteoporosis. Urine markers are being used to reduce the use of bone densitometry and
plain films of the vertebrae as a means of evaluating bone integrity and bone loss, as both have the disadvantage of exposing the patient
to radiation. See Bone densitometry in Appendix 2.
Oxygen saturation: The measurement of the blood’s capacity to transport oxygen, which is a normal part of a blood gas profile.
Oxygen saturation can be estimated from arterial blood samples obtained from a direct arterial puncture (e.g. brachial, femoral, or
radial artery). Normal values are 95-98% arterial, 60-80% venous.
pH of blood: Living systems function in a “buffered” fluid environment that is usually close to a neutral pH (i.e., neither too acid nor
too alkaline) which, in the blood stream, is between pH
7.35 and 7.45. The body compensates for changes in pH – which are related to the quantity of carbon dioxide and hydrogen ions
in the body – by altering the activity of the lungs and/or kidneys. A decrease in serum pH may be due to an increase in hydrogen
ions or to a decrease in compensating carbonate ions and is known as acidosis. An increase in serum pH may be due to a decrease
in hydrogen ions or an increase in carbonate ions and is known as alkalosis. Acidosis and alkalosis are categorized according to
cause. That attributed to decreased pulmonary activity with accumulation of carbon dioxide is known as respiratory acidosis, and
that attributed to increased pulmonary activity with decreased carbon dioxide is known as respiratory alkalosis. Decreased excretion of
acids by the kidney is termed metabolic acidosis; increased renal excretion of acids is metabolic alkalosis. The pH is needed to
diagnose these conditions, and is usually obtained by arterial puncture.
pH of urine: Urinary pH has a wider range than blood pH because the kidneys have a major role in maintaining the pH in the
circulation close to neutral (pH 7.35-7.45). If the pH in the blood falls and becomes more acid, the kidneys increase the excretion of
hydrogen ions (acids). If the pH in the blood rises and becomes more alkaline, the kidneys increase the excretion of bicarbonate ions
(alkalines).
Phosphorous (phosphates, PO4): Phosphorous is the predominant intracellular anion (negative ion), and is integral to the storage
and utilization of energy. It regulates calcium levels, carbohydrate and lipid metabolism, acid-base balance, and is essential to hone
formation. Approximately 85% of the body’s phosphorous and phosphates are found in bone.
Pituitary function test: A general term for any laboratory test used to evaluate the function of the anterior pituitary. Pituitary
function tests can be static, that is, the level of a pituitary hormone (e.g. ACTH) and linked feedback hormone (cortisol, which is
secreted by the adrenal gland in response to ACTH) are measured in the serum; or dynamic, where hormones are administered to
evaluate the response of the feedback organs to stimulation by hormones of the anterior pituitary (adenohypophysis). Dynamic tests
include the combined anterior pituitary test, insulin tolerance test, and glucose tolerance test.
Plasmin: An enzyme formed in from plasminogen that is responsible for the removal of blood clots. Plasmin exists in free and bound
forms. There is no direct measurement of plasmin because of its instability. See Plasminogen
Plasminogen: A proenzyme present in the circulation, which is synthesized in the liver and produced or stored in eosinophils. It
forms complexes with fibrinogen and fibrin. During coagulation, large amounts of plasminogen are incorporated in the fibrin mass or
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clot. The most common indication for measuring plasminogen is suspected disseminated intravascular coagulation, a serious clinical
condition in which it is markedly decreased.
Platelet count: The enumeration of circulating platelets, which are largely responsible for the clotting of blood. See Complete blood
count (CBC).
Potassium (K+): Potassium is the main positive ion (cation) in cells, is critical in the synthesis of new molecules, and involved in energy
transfer. Potassium in the circulation has a narrow range, and both extremely high and low levels may be fatal. Potassium is usually
performed as part of a chemistry profile.
Protein (urine): Normal urine contains little significant protein. An increase in normal protein or simply protein in the urine
(proteinuria) is usually caused by kidney disease. An increase in abnormal proteins (monoclonal proteins) is usually caused by
neoplasms (multiple myeloma or lymphomas).
Pyruvate kinase: An enzyme that participates in the anaerobic metabolism of glucose. Its absence is the most common cause of
congenital hemolytic anemia. It is measured in the evaluation of chronic hemolytic anemias. A decrease in pyruvate kinase is noted in
hemolytic anemias, acute leukemias, and aplastic anemia.
Red blood cell count: The number of red blood cells per volume of blood. See Complete blood count (CBC).
Red blood cell distribution width (RDW): An estimation of erythrocyte anisocytosis, (presence in the blood of red blood cells
showing excessive variation in size); a value generated by automated red blood cell counters. This parameter is used to determine the
cause of a given anemia.
Red cell indices: A group of values obtained from automated blood cell counters that provide information about the size and the
concentration of hemoglobin in red blood cells (i.e. MCV, MHC, and MCHC). See Complete blood count (CBC).
Reticulocyte count: Reticulocytes are immature red blood cells that lack a nucleus and are present in extremely low numbers in the
peripheral circulation. The reticulocyte count is a simple way of evaluating the rate of RBC production and the response of the
bone marrow to anemia.
RIA (radioimmunoassay): A method that measures antigens or antibodies based on competitive inhibition of the binding of
radioactively labeled antigens with the binding of unlabeled antigens to specific antibodies. RIA allows measurement of
minimalamounts of antigenic substances, including enzymes and hormones, and is widely used in research as it is relatively easy to
design an assay to detect a substance of interest. RIAs are being phased out of the clinical laboratory in favor of enzyme,
fluorescence, or chemiluminescence assays, which eliminate the waste disposal problems inherent in maintaining radioactive
materials.
Sodium (Na+): An electrolyte which is the primary positive ion (cation) in extracellular fluids and in the circulation. It is critical in
homeostasis of body fluids, conductance of neuromuscular impulses, and enzyme activity. Serum and urine levels may be
measured.
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Transferrin: A protein that is a carrier of iron in the circulation.
Transferrin levels correspond to the maximum amount of iron that can be bound to the protein, a value that is designated “total ironbinding capacity” (TIBC). Transferrin levels may be requested in the presence of suspected iron-deficiency anemia, or in chronic liver
disease, renal failure, malnutrition, lead poisoning, and other conditions. Transferrin levels are increased in severe iron deficiency
anemia, and may be decreased in severe illnesses such as liver disease, cancer, iron overload, and severe malnutrition.
Uric acid: A small breakdown product of purines, which are part of DNA. Uric acid is excreted primarily by the kidneys, as well as by the
gastrointestinal tract. Increased uric acid crystals are deposited in various tissues: knee, elbow, ankle, and particularly the “big toe” joint
are favored areas. “Gout” is the general term used for the inflammatory and very painful condition caused by uric acid crystal
deposition in joints. Uric acid increases with rapid cell turnover, such as cancer (particularly during chemotherapy for cancer where
there is large amount of cell death), also as a result of drug therapy (diuretics in particular), and in many other conditions.
Varicella-zoster virus (chicken pox): A virus that belongs to the herpes family of viruses; it is classified as human herpesvirus-3. The
primary or childhood form, chicken pox, presents in characteristic fashion, commonly as a wave of itchy vesicles that spread over the
entire body, healing within three to five days. Of greater concern is first-time exposure to the varicella-zoster virus (VZV) as an adult,
who lacks protective antibodies. Antibodies can be detected within one to four days of acute infection.
Viscosity: Viscosity is the resistance to the flow of a fluid, e.g. the thickness of the blood, or the ease with which it flows in the
circulation.
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APPENDIX 2: MEDICAL PROCEDURES
Biopsy: A general term referring to the surgical procedure in which a small piece of tissue is removed from a patient and the tissue itself.
The changes present in the tissue are interpreted by a pathologist, who renders a diagnosis based on relatively standardized criteria.
Biopsies are used to diagnose a disease; determine the extent of a disease (e.g. metastasis in cancer); and determine the adequacy of
surgical removal.
Bone densitometry: The measurement of bone mass or density to assess bone strength or density, which is reduced in patients with
osteoporosis (bone loss). The most common method of assessing bone density is by dual-energy X-ray absorptiometry (DEXA) scan.
Bone density is decreased in estrogen deficiency, osteopenia, long-term steroid therapy and parathyroid disease.
Bone marrow aspiration and biopsy: Bone marrow is the soft tissue found in the middle of certain bones (hip and pelvis,
sternum, spinal vertebrae, amongst others) and is the site where red blood cells, white blood cells, and platelets are produced.
Bone marrow aspiration and biopsy is obtained when there is a need to explain an abnormal finding relating to an individual’s red
blood cell, white blood cell, or platelet count. This procedure can also performed when a physician wishes to assess the status of a
known hematological disease; determine if treatment is required; determine if a treatment for a known disorder requires further
modification; or to simply assess the result of a particular treatment (e.g. after chemotherapy). The procedure is either performed
in a physician’s office with local anesthesia, or can be performed in a more monitored setting under light sedation. Bone marrow
biopsies are usually obtained from the posterosuperior iliac spine (posterior upper aspect of the hip bone). The skin is cleaned with an
antiseptic solution, and the area is anesthetized using local anesthetic. A large-bore needle is inserted, and for the aspiration a fluid
specimen in which bone marrow is suspended is removed. For a biopsy specimen, a solid core of marrow cells accompanied by bone is
removed. The resulting specimens are evaluated by a pathologist and a diagnosis is rendered thereafter. Specialized tests can be
performed, such as flow cytometry, with the aspiration and biopsy specimens. Discomfort from the procedure varies among patients;
most individuals will note deep aching bone pain during the procedure and for a few days afterwards – hence the popularity of having
the procedure done under light sedation if available.
Bone scan: A radiological nuclear medicine procedure in which a radioactive compound is administered through an intravenous line;
the distribution of the radioactive compound throughout the body’s entire skeleton is analyzed a few hours after administration by a
specialized gamma camera for increased or decreased uptake of the compound. Normal bone has a low level of diffuse uptake; local
sites of increased or decreased uptake of the radioactive compound may indicate primary or metastatic cancer, infection, arthritis,
trauma and metabolic bone disease.
Bronchoscopy: A procedure where the physician uses a flexible fiberoptic instrument to visualize the upper airways, vocal cords, and the
tracheobronchial tree. Solid tissue biopsies, bronchial washings(aspiration of a small amount of saline fluid instilled in the area of
concern for capture of cells, organisms, or other material), and administration of drugs or devices can be performed. The patient is
usually mildly sedated and monitored very carefully. Biopsies and bronchial washings are evaluated following the procedure.
Computed tomography (CT scan): A radiologic procedure that uses narrow X-ray beams to examine body sections from many
different angles and produces a precise image of that area. CT scanning results in a thousand fold increase in the sharpness of
images of a body region and can often pinpoint abnormalities measuring less than 2 mm. The images obtained are based on the
simple principle that different tissue densities (fat, water, air, muscle, bone) will have a different appearance on the film. The CT
scan is noninvasive and can be performed with or without contrast medium (x-ray dye). Contrast material help outline blood vessels
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and kidney function (IV contrast), whereas oral contrast helps better define the hollow organs such as the stomach and
intestines.
Electromyography (EMG): Electromyography measures minute electrical discharges produced in skeletal muscle both at rest and
during voluntary contraction and are used in the diagnosis of neuromuscular disease. The electrode for EMG is inserted through
the skin, and the resulting electrical discharge or motor unit potential is recorded. Nerve conduction studies, which constitute a
separate diagnostic protocol, can be performed simultaneously. Nerve conduction studies measure the speed at which nerves carry
electrical signals and are often used to diagnosed peripheral neuropathy, as well as carpal tunnel syndrome.
Fine needle aspiration (FNA): A method of diagnostic cytology and pathology using a thin needle to obtain cells and minute tissue
fragments for examination by light microscopy. The sites selected for FNAs are often guided by radiologists with fluoroscopy, computed
tomography, ultrasound, or MRI.
Fluorescein angiography: A technique used to diagnose chorioretinal disease based on the enhancement of anatomic and vascular
details in the retina after intravenous injection of fluorescein. The distribution pattern of the fluorescein dye can be viewed and
photographed with a fundus camera as a function of its intrinsic fluorescence.
Fluoroscopy: An X-ray imaging technique used to evaluate moving lung and heart structures predominantly, and to help identify the
location of tissues and suspicious masses being biopsied. Fluoroscopy has the disadvantages of exposing patients to more radiation
than routine radiologic examinations and of overlooking small lesions, and there is no permanent record made of the images
produced.
Fundoscopy (Fundoscopic examination, Ophthalmoscopy): The examination of the back of the eye (fundus) with an
ophthalmoscope, which is part of the routine examination of a patient. Ophthalmoscopy allows a magnified evaluation of the blood
vessels, nerves, and retina. Retinal hemorrhages, retinal detachments, swollen blood vessels as is the case in patients with elevated
serum viscosity, and other abnormalities can be easily viewed using this technique.
Gallium scan: A radioscintillation method in which 67Gallium citrate is injected intravenously, and images of its pattern of distribution
are obtained. Once injected, gallium binds primarily to transferrin and to any tissue that also concentrates lactoferrin. The gallium scan
was once used to localize abscesses, osteomyelitis, and other infections, and continues to be used for staging lymphomas, lung cancer,
hepatoma, melanoma, metastases (to bone, brain, lung), and many types of primary cancers.
High-resolution computed tomography: A CT scan study at slice width of 4 mm or less, which is narrower than the usual 1-3 cm
interval slices obtained in conventional CT imaging. HRCT is the optimal technique for evaluating interstitial lung disease and
emphysema and is preferred to conventional CT in detecting subpleural nodules, small linear densities and bronchiectasis and is of use
in any body region where great detail is desired.
Immunoelectrophoresis (IEP): A technique used to detect abnormal proteins (immunoglobulins) in serum and urine. IEP is used to
evaluate monoclonal gammopathies, but essentially has been replaced by immunofixation electrophoresis. See Electrophoresis in Appendix 3.
Intravenous pyelography (IVP): A radiocontrast study in which radiocontrast is administered intravenously and excreted by the
kidneys as a means of evaluating the morphology and function of the urinary tract. The procedure is a series of timed X-ray images that
are obtained before, during, and after intravenous administration of contrast and subsequent excretion by the kidneys. A wide range
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of anatomic defects can be detected by IVP, including kidney and bladder tumors and obstruction of the ureters by kidney stones for
example.
Laparoscopy: The laparoscope is a small, flexible instrument equipped with an optical lens. It is used diagnostically to view various
internal organs and obtain biopsies from the liver, ovaries, and elsewhere by inserting it through a small incision in the anterior abdominal
wall. It can also be used therapeutically to perform procedures such as lysis of intra-abdominal and/or pelvic adhesions, tubal
sterilization, removal of foreign bodies, and other types of minimally invasive surgery such as laparoscopic cholecystectomy
(gallbladder removal), hysterectomy, and oophrectomy (removal of ovaries) amongst others. Laparoscopic visualization of the intraabdominal organs permits evaluation of symptoms, and obtaining tissue biopsy specimens when warranted. Laparoscopy has replaced
laparotomy in many cases. Laparotomy is reserved for instances when more extensive surgery is being considered. Most laparoscopic
procedures are done under general anesthesia; some procedures can be done under local anesthesia.
Laryngoscopy: The laryngoscope is a small, flexible fiberoptic tube similar in its basic design to other endoscopes. It is threaded down
the throat and used to view (and biopsy) laryngeal structures. The procedure is done under local anesthesia in the overwhelming
majority of cases.
Lumbar puncture (spinal tap): A diagnostic procedure in which a needle is inserted into the subarachnoid space between the third
and fourth lumbar vertebrae of the spinal column to obtain cerebrospinal fluid (CSF) for analysis. A lumbar puncture may rarely be
used to evaluate intracranial pressure. A lumbar puncture is almost always preceded by an X-ray of the spine, and a CT scan of the brain (in
cases where elevated intracranial pressure is suspected).The procedure is performed in the hospital or clinic under sterile conditions. A
long needle is inserted at the L4-L5 vertebral interspace and subarachnoid (cerebrospinal) fluid is obtained. The fluid is sent to the
laboratory for analysis of chemistry (i.e. glucose, proteins), to microbiology for culture if infection is suspected, and to
cytology/pathology to evaluate the cellular elements.
Lung volumes: Part of a series of procedures (see pulmonary function test) in which the lung may be functionally divided into air
“compartments” such as: (1) expiratory reserve capacity: the maximum volume of air that can be voluntarily exhaled; (2) functional
residual capacity: volume left in the lungs at the end of a normal breath which is not normally part of the subdivisions; (3) inspiratory
capacity: the maximum volume that can be inhaled; (4) inspiratory reserve capacity: the maximum volume of air that can be inhaled
above the tidal volume; (5) tidal volume: the normal to-and-fro respiratory exchange volume; (6) total lung capacity: the entire
volume of the lungs, about 5 liters; (7) vital capacity: the maximum volume that can be inhaled and exhaled.
Lymphangiography: Lymphangiography consists of a radiologic examination of the lymphatic system in which an oil-based
radiocontrast medium is injected into the foot or hand. The feet are used to examine the lymphatic circulation of the legs, inguinal
and iliac regions, and retroperitoneum to the thoracic duct. Injection into the hands visualizes axillary and supraclavicular lymphatic
circulation and lymph nodes. Lymphangiography is used primarily to diagnose and monitor treatment of lymphomas. Fluoroscopy is
used to monitor the filling of the lymphatic vessels.
Mediastinoscopy: An invasive surgical procedure in which a flexible endoscope is inserted through a hole in the superior mediastinum
(anterior chest) through a hole in the chest wall, and the regional structures (lungs, lymph nodes, pericardium) are examined visually
to detect the presence of masses, neoplasms, or other lesions. If structural abnormalities are identified, they are biopsied and sent
to the laboratory for further study. Mediastinoscopy is also performed sometimes as part of a “staging procedure” when the patient
is known to have a malignancy. In such cases, it is used to determine how far the tumor has spread, which will determine the type of
therapy recommended by the oncologist.
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MRI (magnetic resonance imaging): A noninvasive diagnostic technique that is based on fundamental principles of physics. The
hydrogen ions in the human body are subjected to a highly controlled, high-intensity radiofrequency magnetic field. The patient’s
hydrogen ions respond by emitting a radiofrequency signal that is then processed by computer to produce an image on film or
computer. MRI has the following advantages over computed tomographic imaging (CT scan): (1) it does not produce ionizing
radiation; (2) the difference between normal and pathological tissue is greater; (3) confusing bone artifact do not occur; (4) rapidly
moving components appear dark, and blood flow through large vessels can be analyzed as a type of natural contrast. Images are
produced by passing the patient through a tubular structure/device that generates a powerful electromagnetic field.
MRA (magnetic coronary angiography): A form of MRI used to identify clinically important abnormalities in arteries, typically either
the heart or brain arteries. The procedure is similar to a standard MRI.
Myelography: A radiologic technique for examining the spinal canal, in particular the lumbar region. Myelography is used to
evaluate spinal cord defects due to compression of the spinal cord and/or its roots by a herniated disk, degenerative articular lesions,
trauma, tumors, or other masses of the spinal cord or meninges or metastases, multiple sclerosis, or increased intracranial pressure.
The procedure consists of the insertion of a long spinal needle through which a radiocontrast is injected. The images are obtained by
fluoroscopy and X-rays, using a tilting table.
Nerve biopsy: A biopsy used to evaluate primary or secondary neuropathies or systemic diseases like amyloidosis. Various special
studies can be done on a properly obtained nerve biopsy, including biochemical analysis, electron microscopy, histology,
immunochemistry, various molecular studies, and virology. The site selected for the nerve biopsy is critical and should come from an
area of active disease. The sural nerve at the lower part of the leg is the preferred site for the peripheral neuropathy associated with
Waldenstrom’s macroglobulinemia.
Nerve conduction study: A noninvasive method for assessing a nerve’s ability to carry a neural impulse and its speed of transmission. In
these studies, larger peripheral motor and sensory nerves are electrically stimulated at various intervals along a motor nerve.
Typically, two metal plates are placed on the skin at a distance from each other. An electrical stimulus passes through one plate
and causes the nerve to fire, resulting in a “compound” muscle action potential that can be measured and recorded.
Nuclear scanning (radionuclide imaging): Any number of diagnostic procedures in nuclear medicine (commonly known as “scans”, as
in bone scan, liver scan, thyroid scan, PET scan) hat use a substance containing a radioactive isotope. The amount of radioactivity in
the isotopes used in diagnostic medicine is minimal and poses no threat to health. The body flushes out the radioactive ions within hours
to days after the study’s completion.
Occult blood testing (stool for occult blood): The testing of stool for the presence of bleeding that is not apparent to the naked
eye (usually more than 50cc per liter of stool is required to visually recognize blood in the stool) to detect possible malignancy. Patients
should not consume vitamin C for one to three days before occult blood testing. A high-fiber, red meat-free diet with restriction of
peroxidase-rich vegetables (e.g. broccoli and cauliflower) has been recommended for 72 hours before testing. Alcohol, aspirin, and
non-steroidal anti-inflammatory drugs can cause false positive results. Fecal blood is detected primarily by the guaiac method, a low-cost
screening technique that uses a guaiac-impregnated paper to indirectly measure hemoglobin by measuring the activity of an enzyme,
pseudoperoxidase. While sensitive, the guaiac test is nonspecific; false-positive results are common. The unexplained presence of
anemia in a patient is virtually always evaluated with occult blood testing (as well as other simple routine tests) as part of the initial
evaluation, as the gastrointestinal tract is an important source of unexplained blood loss. New and easy stool screening tests can be
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performed at home and sent to the laboratory with minimum fuss. Three specimens should be submitted for the most reliable
interpretation.
Partial thromboplastin time (PTT): The PTT test is used in preoperative screening for increased bleeding tendencies and to
monitor therapy with heparin and oral anticoagulants, drugs used to decrease clot formation. The PTT test evaluates the time
required for the clotting proteins or coagulation factors to form a fibrin clot. PTT values may be increased in liver disease, leukemia,
lymphoma, coagulation deficiencies, drugs and other disorders.
Positron emission tomography (PET scan): A technique used to measure the functional activity of a particular region of the body –
heart, lungs, brain, etc. – in which a radiopharmaceutical is injected into the patient and is absorbed by tumor cells. Measurement of
functional activity are determined by concentration of the radiopharmaceutical, then fed into a computer, which produces a colorcoded moving picture or a gray-scale image of the region. PET is useful for precisely locating a tumor and for evaluating a tumor’s
response to chemotherapy and radiation treatment.
Pulmonary function test (PFT): A general term for any of a group of techniques and maneuvers that provide information on
pulmonary function. These techniques include spirometry, ventilation and perfusion scans, and measurement of lung volumes, airway
resistance, carbon monoxide diffusing capacity, and arterial blood gases. Pulmonary function tests per se are used to measure the
volume of air that can be inhaled, the efficacy of gas exchange, and the strength of exhalation.
Pulse oxymetry (oxygen saturation test): A noninvasive method for assessing the oxygen saturation (SaO2) or arterial blood in a
continuous fashion. A pulse oxymeter senses the optical differencebetween oxyhemoglobin and deoxyhemoglobin and detects the
differences as increased or decreased transmission of light as the blood pulses through tissue. The probe is most commonly placed on
the earlobe or finger.
Punch biopsy: A minor surgical procedure performed on an outpatient basis in which a hollow needle is used to obtain a 3-, 4-, or
rarely 6-millimeter in diameter core (“punch”) of tissue, almost invariably of skin, which is then evaluated by light microscopy and other
tests.
Radioactive iodine uptake (thyroid scan): A method used to determine the functional status of the thyroid gland using a
radioactive isotope of iodine. The most common procedure is the
24-hour uptake, in which uptake of iodine is measured for 24 hours after administration. Iodine-131 is injected intravenously.
Spirometry: The measurement of the movement of air in and out of the lungs during various breathing maneuvers, as a means of
preoperative evaluation of pulmonary function. Spirometry is the most important of the pulmonary function tests.
Technetium-labeled red blood cell scintigraphy: A noninvasive method for identifying the site of slow or intermittent
gastrointestinal hemorrhage. Red blood cells that have been labeled with technetium are injected in the circulation and images are
obtained with a gamma camera, which detects scintillation and identifies areas of increased radioactivity, hence areas of suspected
bleeding.
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Thoracentesis (pleural fluid tap): The drainage of fluid for therapeutic or diagnostic purposes from the pleural space using a long
needle. Once obtained, the fluid is analyzed for chemical composition, and the cells are examined by a pathologist. Thoracentesis
is used in determining the nature (i.e. benign or malignant) of a collection of fluid identified clinically or radiologically in the
pleural space.
Tonometry: A technique that measures intraocular pressure (in mm Hg) by contact (indentation of or applanation on) or noncontact
(by a puff of air) on the eyeball. Tonometry is used to diagnose and manage glaucoma and ocular hypertension, and in routine ocular
examination. Normal intraocular pressure ranges from 15 to 20 mm Hg.
Tzanck test: A rapid method for determining the nature of cells in blistering diseases of the skin (e.g. herpesvirus lesions).
Ultrasonography: A diagnostic method that generates images based on the differences in the ability of tissues of various densities to
slow ultrasound waves. Electricity applied to a piezoelectric crystal or ceramic in a “transducer” causes a high frequency (2.25-5.0
MHz/s) mechanical vibration, which emits sound in the form of “pressure waves”. These waves are transferred into tissues and
organs, and at each tissue interface, apportion of the ultrasound wave is reflected, generating echoes. As the echoes return in the
direction of the transducer, there is a slight distortion or deformity of a piezoelectric crystal in the transducer, which produces minute
voltage pulses that are amplified and displayed in one of several “modes”: 1) A-mode display ultrasonography provides simple
displays that are plotted as a series of peaks, the height of whichrepresents the depth of the echoing structure from the transducer;
2) B-mode ultrasonography yields two-dimensional tissue “slices” that are produced using different types of transducers, capable of
scanning sequentially across a limited region or finite space. This method has a wide range of applications, including imaging of the
fetus in obstetrics, imaging of the kidneys, gallbladder, heart structures, etc.; 3) Duplex ultrasonography in a modality that
combines the standard real-time B-mode display with pulsed Doppler signals, allowing analysis of frequency shifts in an
ultrasonographic signal, which reflect motion within a tissue (e.g. blood flow). This method is useful in evaluating atherosclerosis of the
carotid arteries, and other circulatory disturbances; 4) M-mode display ultrasonography is a modality in which the echo signal is
recorded on a continuously moving strip of paper, with the transducer held in a fixed position over the aortic or mitral valves. Each
dot on the display represents a moving structure; stationary structures are represented as straight lines. M-mode was the first display
to be used in ultrasonography and correlating heart valve motion with electrocardiography, phonocardiography, and Doppler
echocardiography. The side-effects of ultrasonography are minimal because the energy levels for diagnostic imaging are considered too low
to produce tissue destruction or major disturbance.
Upper gastrointestinal endoscopy (upper GI scope): One of the most commonly performed endoscopic procedures, this technique
allows the physician to examine and obtain diagnostic material from the mucosal surface of the upper gastrointestinal tract,
from the esophagus to the upper part of the small intestine. The procedure consists of the insertion of a long fiberoptic endoscope
by mouth and the patient is usually sedated with intravenous mediciation and supplemented with oxygen during the
procedure.The patient is monitored continuously during the procedure; in this regard, the procedure has a long track record of being
very safe in experienced physicians.
Upper GI study (barium swallow, ES&D): A general term for radiologic studies in which a contrast medium is administered in the
upper gastrointestinal tract (esophagus, stomach, duodenum) and images obtained. “Double contrast” studies are used to evaluate
mucosal abnormalities. “Single contrast” studies are best suited for identifying gastric outlet obstruction, gastroesophageal reflux
disease, hiatal hernia, and esophageal varices or cancer in the esophagus. The procedure consists of administration of a barium
solution (“milkshake”) and evaluation of its flow through the esophagus, stomach, and duodenum by fluoroscopy; periodic radiologic
films are taken by conventional imaging devices.
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Urea breath test: A noninvasive test used to identify active Helicobacter pylori infection. In the test, 13C or 14C is ingested. If enough
urease (presumed to be of H. pylori origin) is present, radiolabeled carbon dioxide will be absorbed into the blood and excreted in
the breath. Breath is collected before the test as a baseline and after the ingestion of the labeled urea. Detection of active or past H.
pylori infection is done most often by simple blood test these days, whereas the urease breath test is used to confirm eradication of the
H. pylori organism.
Urinalysis: A low-cost test in which a urine specimen is examined in order to screen for various diseases. Routine urinalysis is used to
detect renal disease (e.g. glomerulonephritis), urinary tract disease, or metabolic disease like diabetes mellitus.
Ventilation-perfusion scan (V/Q scan): A noninvasive radionuclide study of the ratio of pulmonary ventilation (V) to pulmonary
blood flow (perfusion, Q) through the lungs. The V/Q scan is used to detect pulmonary embolism (blood clot to the lung). In a
commonly used protocol, the scan is performed after inhalation of 133Xe and intravenous 99mTc, which allows evaluation of inspiratory
airflow, lung volume, presence of air trapping, and adequacy of perfusion.
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APPENDIX 3: LABORATORY PROCESSES
Cytology: The science that studies the formation, structure, and function of cells; the main purpose is to detect early, curable
malignancy, as well as viral, fungal, and other infections. The term cytology also refers to the microscopic examination of body tissues or
fluids for the detection of disease.
DNA hybridization: A technique for detecting the presence of a specific segment of “target” DNA.
Electrophoresis: The separation of proteins according to the amount that they migrate when subjected to an electrical current. See
Protein electrophoresis.
Erythrocyte sedimentation rate (ESR, Set Rate): The ESR is a simple laboratory test that measures the rate at which red blood cells
in well-mixed venous blood settle to the bottom of a special test tube. This serves as a nonspecific indicator of inflammation and
should be performed within a few hours (12) of obtaining the blood specimen. Although it is routinely ordered by many
physicians, it is nonspecific, and inflammation is better monitored by serial measurement of C-reactive protein. Note that anemia and
paraproteinemia (such as is often the case in WM) almost always invalidate the results.
Mercaptoethanol agglutination inhibition test: A laboratory test used to separate IgG and IgM as the cause of an agglutination
reaction. When a patient is exposed to bacteria or virus, the immune system responds by producing immunoglobulins, which are
at first relatively nonspecific and often IgM; if the infection is chronic, the IgG is more elevated than the IgM. Treating IgM
antibodies with mercaptoethanol abolishes its agglutination reaction and ability to bind complement. This test is a necessary step in
immunoelectrophoresis.
Nephelometry: A technique that measures the concentration of substances by means of light scattering by the suspended particles. It
is most commonly used to detect immune complexes when the precipitating antigen or antibody is unknown.
Ploidy analysis: A technique in flow cytometry that evaluates the chromosomal content of cells, which is a marker for aggressiveness in
malignancy. In general, diploidy (i.e. the presence of two haploid sets of chromosomes) is a normal or near-normal state. In contrast,
anaplastic and aggressive tumors are more often aneuploid or hyperdiploid. Hyperdiploid tumors have a high relapse rate and
behave aggressively, resulting in a shortened survival. The same “rule” (diploid, good prognosis; aneuploid, poor prognosis) applies to
lymphoma and many other tumors.
Protein electrophoresis (SPEP, SPE, serum protein electrophoresis): Protein electrophoresis is a screening method for detecting
significant serum protein abnormalities. When submitted or electrophoresis, the proteins are divided into prealbumin, albumin,
α1 and α2, β, and γ zones. One or more regions of the protein electrophoresis may be increased or decreased in conditions that affect
the production of certain proteins, or variable in the presence of gene polymorphism. The interpretation is complex and any
abnormality identified should be confirmed by re-running the electrophoresis. The body fluid of interest is placed on a gel, and an
electric current is placed at one end. The proteins migrate to certain points, depending on their weight and electric charges.
Prothrombin time (PT, Pro-time): A coagulation test used to determine the time needed to form a blood clot, evaluate the
blood’s clotting capacity, and evaluate the functional activity of coagulation factors. PT is most often used to monitor therapy with
oral anticoagulants, in particular with warfarin (Coumadin).
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Radioimmunoprecipitation assay: This laboratory technique identifies antibodies to specific viral antigens. Disrupted, purified virus
previously grown in culture with a radioactive amino acid is incubated with a test sample which may contain an antibody against
the viral antigen. The proteins in the sample are then separated by electrophoresis.
S phase analysis: Analysis of the fraction of the cells in a tissue or fluid that are a ctively synthesizing DNA, which provides useful
information on a tumor’s rate of proliferation. The S phase fraction is best measured by flow cytometry and is a parameter often
measured when evaluating certain malignancies. S phase analysis provides information on how frequently the cells in a lesion are
dividing, not on whether it is benign or malignant.
T3 uptake test (triiodothyronine uptake assay): A test that indirectly measures free thyroxine (T4) as a reflection of the tyroid
function, which corresponds to the amount of T3 (triiodothyronine) that can be bound to carrier proteins, in particular to thyroxinebinding globulin (TBG). In the T3 uptake test, a known amount of radioactive T3, which is greater than the normal binding capacity of
thyroxine-binding globulin (TBG), and a binding resin are added to the serum. The radioactive T3 that remains after occupying
TBG’s binding sites binds to the resin, which can then be measured by RIA.
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Waldenstrom`s

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