anemia of chronic inflammation. A large MCV indicates a macrocytic cell, which can
be caused by a vitamin B12 or folic acid deficiency. Underlying disease states (e.g.,
habitual alcohol ingestion, chronic liver disease, anorexia nervosa, hypothyroidism,
reticulocytosis, and hematologic disorders) may also present with an elevated MCV
secondary to deficiencies in these vitamins.
34 The MCV can be normal in a patient
with a “mixed” (microcytic and macrocytic) anemia. Note that a direct assessment of
a blood smear by a microscopic examination is the gold standard for confirming RBC
The MCHC is a more reliable index of RBC Hgb than MCH. MCH measures the
weight of Hgb in the RBCs in a sample and MCHC measures concentration of the
RBCs contained within a sample. In normochromic anemias, changes in the size of
RBCs (MCV) are associated with corresponding changes in the weight of Hgb
(MCH), but the concentration of Hgb (MCHC) remains normal. Changes in the Hgb
content of RBCs alter the color of these cells. Thus, hypochromic refers to a decrease
in RBC Hgb, reflected by reduced MCHC, and may indicate iron-deficiency anemia.
Conversely, hyperchromic RBCs have an elevated MCHC because of the presence of
greater amounts of Hgb. Hyperchromic cells are not commonly encountered.
Adults—Reference Range: 0.5%–1.5%of RBCs or 0.005–0.015
Reticulocytes are young, immature erythrocytes and typically comprise about 1%
of the RBCs. The reticulocyte count measures the percentage of these new cells in the
circulating blood. An increase in the number of reticulocytes implies an increased
number of erythrocytes are being released into the blood in response to a stimulus.
Reticulocyte count is a good indicator of bone marrow activity because it represents
a recent production. Because erythrocytes regenerate rapidly, reticulocytosis can be
noted within 3 to 5 days after hemolysis or after a hemorrhagic episode. Appropriate
treatment of anemias caused by iron, vitamin B12
, or folic acid deficiencies should
result in an increased reticulocyte count. Caution must be exercised in the
interpretation of reticulocyte counts. Changes in the number of RBCs will result in
proportional changes in the reticulocyte count because the latter is reported as a
percentage of the number of RBCs.
Erythrocyte Sedimentation Rate
The ESR is the rate (expressed in mm/hour) at which erythrocytes settle to the
bottom of a test tube through the forces of gravity and in response to fibrinogen levels
in the blood. The ESR is a nonspecific value and may be increased abnormally in
acute and chronic inflammatory processes, acute and chronic infections, neoplasms,
infarction, tissue necrosis, rheumatoid-collagen disease, dysproteinemias, nephritis,
and pregnancy. However, ESR can also be affected by changes not related to the
inflammation (e.g., change in erythrocyte size, shape, or number). Laboratory
technique can also affect the sedimentation rate substantially. Because many factors
can enhance the settling rate of RBCs, moderate to marked elevation of the ESR
merely indicates an inflammatory component to a disease state. An increased ESR in
the setting of a normal physical examination is usually transient and is rarely the
harbinger of serious occult disease.
Leukocytes or WBCs comprise five different types of cells. Neutrophils are the
most abundant of the circulating WBCs, followed in order of frequency by
lymphocytes, monocytes, eosinophils, and basophils. The neutrophils, eosinophils,
basophils, and monocytes are formed from stem cells in the bone marrow.
Lymphocytes are formed primarily in the lymph nodes, thymus, spleen, and, to a
lesser extent, bone marrow (Fig. 2-2). Each WBC type has unique function, and it is
best to consider them independently rather than collectively as “leukocytes.”
Ultimately, all WBCs contribute to host defense mechanisms.
Reference Range: 40%–70%of WBC
The terms polys, segs, polymorphonuclear neutrophils, and granulocytes are
synonymous with the term neutrophil in clinical practice. The number of neutrophils
is commonly increased during bacterial or fungal infections, because these cells are
essential in killing invading microorganisms. Whereas the bone marrow increases
production of new leukocytes, there is also an increase in the number of circulating
immature neutrophils (e.g., bands); this phenomenon is commonly referred to as a
“left shift,” which suggests acute bacterial infection.
However, neutrophils are also important in the pathogenesis of tissue damage in
some noninfectious diseases, such as rheumatoid arthritis, inflammatory bowel
Increased neutrophils or neutrophilia can also be
encountered during metabolic toxic states (e.g., diabetic ketoacidosis, uremia, and
eclampsia) and during physiologic response to stress (e.g., physical exercise and
childbirth). Drugs (e.g., epinephrine and corticosteroids) can also cause significant
neutrophilia, primarily caused by demargination from blood vessel walls.
Agranulocytosis and Absolute Neutrophil Count
The condition involving decreased neutrophils, or neutropenia, is defined as a
neutrophil count of <2,000 cells/μL; agranulocytosis refers to severe neutropenia.
The most common causes of neutropenia are metastatic carcinoma, lymphoma, and
chemotherapeutic agents. The degree of neutropenia is often expressed by the
absolute neutrophil count (ANC). The ANC is defined as the total number of
granulocytes (polymorphonuclear leukocytes and band forms) present in the
circulating pool of WBCs and can be calculated as WBC × (% neutrophils + %
bands)/100. Generally, the risk of infection is low when the ANC exceeds 1,000/μL;
however, the risk of infection increases significantly when the ANC is less than
500/μL. The risk of developing bacteremia is increased further as the ANC
decreases to less than 100/μL, a condition commonly referred to as “profound
neutropenia.” The most common causes of neutropenia are metastatic carcinoma,
lymphoma, and chemotherapeutic agents. The reader is referred to Chapter 75,
Prevention and Treatment of Infections in Neutropenic Patients, for a more detailed
Reference Range: 22%–44%of WBC
Lymphocytes constitute the second most common WBC in circulating blood. These
leukocytes respond to foreign antigens by initiating the immune defense system. The
vast majority of lymphocytes are located in the spleen, lymph nodes, and other
organized lymphatic tissue. The lymphocytes circulating in blood represent less than
5% of the total amount in the body.
There are two major types of lymphocytes. T lymphocytes (thymic dependent)
participate in cell-mediated immune responses, and B lymphocytes (bone marrow
derived) are responsible for humoral antibody responses. Therefore, diseases
affecting lymphocytes primarily manifest themselves as immune deficiency disorders
that render the patient unable to defend against normal pathogens (see Chapter 76,
Pharmacotherapy of Human Immunodeficiency Virus Infection) or as autoimmune
diseases in which immune responses are directed against the body’s own cells.
Increased numbers of lymphocytes on a white count differential sometimes
accompany lymphoma (see Chapter 96, Adult Hematologic Malignancies) and viral
infections. A relative lymphocytosis is sometimes encountered when the total
lymphocytes have remained constant despite a decline in the total neutrophils.
Monocytes are formed in the bone marrow and are the precursors to macrophages
and antigen-presenting cells (dendritic cells), which are found in the body’s tissues.
Macrophages and dendritic cells are phagocytic cells that engulf foreign antigens or
dead or dying cells. Dendritic cells also present fragments of antigens to T and B
lymphocytes. Monocytosis may be observed in mononucleosis, subacute bacterial
endocarditis, malaria, and tuberculosis, as well as during the recovery phase of some
Because eosinophils have surface receptors that bind IgG and IgE, they can modify
reactions associated with IgG- and IgE-mediated degranulation of mast cells.
Primary lysosomal granules, small dense granules, and specific or secondary
granules are the three types of granules found within eosinophils. The latter granules
account for most of the biologic activity of eosinophils and are toxic to parasites,
tumor cells, and some epithelial cells.
Eosinophils have phagocytic activity, catalyze the oxidation of many substances,
facilitate killing of microorganisms, initiate mast cell secretion, protect against
various parasites, and play some role in host defense. Eosinophilia is probably most
commonly associated with allergic reactions to drugs, allergic disorders (e.g., hay
fever, asthma, and eczema), invasive parasitic infections (e.g., hookworm,
schistosomiasis, and trichinosis), collagen vascular diseases (e.g., rheumatoid
arthritis, eosinophilic fasciitis, and eosinophilic-myalgia syndrome), and
malignancies (e.g., Hodgkin lymphoma).
During infection or inflammation, basophils leave the blood and mobilize as mast
cells to the affected site and release granules. These granules contain histamine,
serotonin, prostaglandins, and leukotrienes. Degranulation results in an increased
blood flow to the site and may compound inflammatory processes. An increase in
basophils commonly accompanies allergic and anaphylactic responses, chronic
myeloid leukemia, myelofibrosis, and polycythemia vera. A decrease in the number
of basophils is generally not readily apparent because of the small number of these
back pain. The results of the CBC and leukocyte differential are as follows:
Imaging and other blood work was ordered. L.H. is diagnosed with an abscess in her lower back and
WBCs are the host’s chief defense system, and the neutrophil is the main
component of that system. During bacterial infections, the leukocyte count and the
neutrophils are generally increased, and a left shift (increase in bands) may be
noticeable. The percentage of other types of WBCs is decreased proportionately
because the number of neutrophils is increased.
As the infection progresses, the percentage of band cells may decrease as a result
of an increase in the number of neutrophils that have a longer half-life. This decrease
in bands does not necessarily indicate improvement. A decrease in the percentage of
neutrophils with a decrease in the total WBC count is characteristic of effective
The CBC shows a total WBC count of 8,600/μL with 11% eosinophils. What is the significance of this
In the clinical setting, absolute leukocyte counts may be used in conjunction with
normal reference values. Absolute counts are calculated by multiplying the
percentage of each individual cell by the total leukocyte count. Eosinophils are
usually increased in allergic reactions; therefore, a drug-induced hypersensitivity
reaction is a strong probability in L.H., with an absolute count of 946 eosinophils/μL
(i.e., 11% of 8,600 leukocytes). The clinician should be suspicious of an allergic
drug reaction when absolute eosinophil counts exceed 300 cells/μL. Eosinophils may
increase before, after, or concurrent with other evidence of allergy (e.g., rash).
Eosinophilia without evidence of allergy is not sufficient cause to discontinue a
suspected medication unless the eosinophilia is significant (i.e., >2,000 cells/μL). In
addition, the absence of eosinophilia certainly does not rule out an allergic diagnosis
in a patient exhibiting clear clinical manifestations of an apparent allergic reaction.
Thrombocytes, commonly referred to as platelets, are tiny fragments of cells that
assist with normal blood clotting. Platelet testing is included as part of a CBC and is
often ordered along with other coagulation studies to evaluate bleeding and/or
clotting disorders. Decreased platelet counts or thrombocytopenia may lead to
petechiae, ecchymosis, and spontaneous hemorrhage.
Causes include decreased platelet production, accelerated destruction, loss from
excessive bleeding or trauma, dilution of blood samples secondary to blood
transfusion, sequestration secondary to hypersplenism, disseminated intravascular
coagulation, infection, or systemic lupus erythematosus. Malignancy, rheumatoid
arthritis, iron-deficiency anemia, polycythemia vera, and postsplenectomy syndromes
are the most common causes of elevated platelet counts or thrombocytosis.
The control of bleeding depends on the formation of a platelet plug and the formation
of a stable fibrin clot. The formation of this clot depends on the complex interactions
of plasma proteins and clotting factors. The prothrombin time (PT), international
normalized ratio (INR), and activated partial thromboplastin time (aPTT) are used to
diagnose coagulation abnormalities or to monitor the effectiveness of patients
receiving anticoagulation therapy. When used to assess drug therapy, achieving a
value outside the reference range is in fact a therapeutically desirable outcome.
ACTIVATED PARTIAL THROMBOPLASTIN TIME
Reference Range: 22–37 seconds
aPTT measures the time it takes the body to form a clot. aPTT depends on the
activity of factors VIII, IX, XI, and XII (intrinsic pathway) and the factors involved in
the final common pathway of the clotting cascade (II, X, and V). aPTT is commonly
measured to detect bleeding disorders and coagulation deficiencies and monitor
unfractionated heparin therapy. The reader is referred to Chapter 11, Thrombosis, for
more detailed information regarding the use of coagulation parameters in treating and
monitoring thrombotic disorders.
Reference Range: 10–13 seconds
Prothrombin is synthesized in the liver and is converted to thrombin during the
blood clotting process. Thrombin formation is the critical event in the hemostatic
process because thrombin creates fibrin monomers that ultimately assemble into a
clot and stimulates platelet activation. The PT test evaluates the integrity of the
extrinsic and common pathways and directly measures the activity of clotting factors
VII and X, prothrombin (factor II), and fibrinogen. Automated laboratory instruments
measure PT by recording the time required for the blood to clot after a reagent (i.e.,
tissue thromboplastin) has been added to the patient’s blood sample.
INTERNATIONAL NORMALIZED RATIO
Because different labs use different reagents, the PT results obtained from one
reagent cannot be reliably compared with another reagent. Therefore, the INR is used
as a standard unit to report the result of a PT test. The INR is the recommended
method to monitor both the initiation and maintenance of anticoagulant therapy, most
notably warfarin. Individuals who have normal blood clotting and are not on
anticoagulation therapy should have an INR of 1. For patients on anticoagulation
therapy, the target INR (i.e., therapeutic range) is usually between 2.0 and 4.0
depending on the indication and other patient-specific factors. Outside of the
therapeutic range, the higher the INR, the higher the likelihood of bleeding because
the blood is taking longer to clot. Conversely, if the INR is lower, there is an
increased risk of developing a clot. Many factors including medications, diet, alcohol
intake, and certain medical conditions can influence the INR.
The INR is calculated using Equation 2-12, where the prothrombin ratio (PTR) is
the ratio between the patient’s PT and the laboratory’s control PT, and the ISI is the
international sensitivity index. Commercial manufacturers quantify the ISI for the
specific thromboplastin reagent used in each lot and report this information in the
A standard urinalysis includes physical, chemical, and microscopic evaluations to
assist with diagnosis of various urologic conditions. It begins with simple
observation of the color and the gross general appearance of the urine specimen. The
urine pH and specific gravity are then recorded. Formed elements in the urine are
examined microscopically, and the urine is searched routinely for pathologically
significant substances that are normally not present (e.g., glucose, blood, ketones, and
bile pigments). Urine specimens should be evaluated quickly after collection to
minimize unreliable results. The reader is referred to Chapter 71, Urinary Tract
Infections, for a more detailed description of the use of urinalysis in the detection and
monitoring of urinary tract infections (UTIs).
Gross Appearance of the Specimen
The concentrated, first-morning urine specimen is usually analyzed to eliminate
effects of undue dilution as a result of water intake. The color should be slightly
yellow, depending on the degree of dilution, and the appearance should be clear. The
appearance of the urine may reveal clouds of crystals, bilirubin, blood, porphyrins,
proteins, food or drug colorings, or melanin. Discolored urine is abnormal. A red
coloration of the urine may be imparted by blood, porphyria, or ingestion of
phenolphthalein. A brown urine color may be caused by the acid hematin of blood or
from melanin pigments. Excessive excretion of urobilinogen or the effects of drugs
such as rifampin or phenazopyridine may cause a dark orange urine color. A blue to
blue-green color of the urine may result from the systemic administration of
When freshly produced, urinary pH can range from 4.5 to 8 but is mostly acidic
because of metabolic activity. Alkaline urine may indicate an aged specimen,
systemic alkalosis, failure of renal acidifying mechanisms, or infection in the urinary
Urinary specific gravity provides information regarding a patient’s hydration status.
A normal morning urine specimen should have a specific gravity of 1.003 to 1.030.
The upper end of this range is close to the maximal concentrating ability of the
kidney. A value of 1.010 or less supports relative hydration, whereas a value greater
than 1.020 indicates relative dehydration.
Proteinuria is a classic sign of renal injury. If proteinuria is found during the
evaluation of a patient with a nonrenal illness, it suggests that the disease may also
involve the kidneys (i.e., hypertension and diabetes).
excretes 30 to 130 mg/day of protein into the urine.
Protein in a urine sample is generally tested qualitatively on a random urine
sample by a dipstick method and is usually reported on a scale of 0 (<30 mg/dL), 1+
(30–100 mg/dL), 2+ (100–300 mg/dL), 3+ (300–1,000 mg/dL), and 4+ (>1,000
mg/dL). A positive qualitative test for urine protein should be repeated after a few
days because transient proteinuria can accompany various physiologic and
pathologic states, even when kidney function is normal. Therefore, patients with
CHF, seizures, or febrile illnesses and normal renal function need not undergo
invasive renal function tests if the proteinuria is modest and likely to be transient.
Another qualitative evaluation of proteinuria can be performed in about 2 weeks to
confirm the diagnosis of transient proteinuria.
If subsequent qualitative test results
are positive, a 24-hour urine sample should be collected to quantitatively test for
protein and creatinine (see Creatinine Clearance section). In patients with a normal
24-hour urinary protein concentration, previous positive qualitative test results
probably represent either false-positive results or a transient phenomenon.
laboratory parameter being used with increased frequency to assess proteinuria is the
urine albumin to urine creatinine ratio (UACR). This measurement tends to be less
influenced by fluctuations in urine concentration and may offer a more reliable
indication of proteinuria. UACR values are typically less than 30 mg/g; patients with
values between 30 and 300 mg/g are considered to have microalbuminuria, and
UACR values greater than 300 mg/g indicate macroalbuminemia.
The urine sediment is examined for RBCs, WBCs, casts, yeast, crystals, and
clotting disorders, some collagen diseases, and various bladder, urethral, and
prostatic conditions may cause microscopic hematuria. In women, vaginal blood
occasionally contaminates the urine specimen, but the presence of numerous
squamous epithelial cells should be sufficient to alert clinicians to this artifact.
WBCs should be virtually absent in normal urine, although up to 5 WBCs/HPF
would still be in the reference range. The presence of WBCs in the urine (pyuria)
usually suggests an acute infection in the urinary tract. Some noninfectious
inflammatory diseases of the kidney, ureter, or bladder may also contribute WBCs to
Casts may be used to identify the location of disease in the genitourinary tract.
Casts are composed of proteinaceous or fatty material that outlines the shape of the
renal tubules where they are deposited. The presence of casts must be interpreted in
light of other factors related to the kidney and its function; however, fatty casts, RBC
casts, and WBC casts are always significant. RBC casts usually suggest glomerular
injury, and WBC casts suggest tubular or interstitial injury. Lipid casts with
proteinuria are characteristic findings in patients with nephrotic syndrome or
43 The finding of hyaline casts alone in the presence of proteinuria
suggests a renal origin for the protein. Hyaline or granular casts alone, however, only
suggest some defect in factors that affect cast formation and are therefore difficult to
Crystals may originally appear as a cloud in the urine. Their formation is pH
dependent, and they often appear only as the urine cools to room temperature or in
concentrated urine. In acidic urine, crystals may be uric acid or calcium oxalate; in
alkaline urine, they may be phosphates. Crystals per se are not highly significant,
although they may reflect a tendency toward the formation of renal calculi.
and Gram stain indicate the following:
Urine WBC: too numerous to count (TNTC)
Squamous epithelial: few per HPF
Gram stain: numerous Gram-negative rods
What objective data from the urinalysis indicate a UTI?
The cloudy appearance of S.T.’s urine indicates the presence of bacteria, protein,
and WBCs, which is supported by the urinalysis results. The lack of a significant
UTI involving Gram-negative organisms (most likely Escherichia coli that causes a
CASE 2-6, QUESTION 2: What objective data from the urinalysis indicate uncontrolled diabetes?
Glucose is normally filtered in the glomerulus and a majority is reabsorbed in the
proximal tubule of the kidney. S.T.’s glycosuria (4+ glucose) and fingerstick of 415
mg/dL indicate the filtered amount of glucose exceeds the capacity for reabsorption
(˜180 mg/dL). Additionally, the presence of positive ketones indicates the body is
utilizing fat, not glucose, for energy. High levels of ketones can predispose S.T. to
dehydration, resulting in diabetic ketoacidosis.
Many drugs have a wide dosing range that can achieve efficacy with low risk of
toxicity. Drugs that have a narrow dosing range with high risk of toxicity (narrow
therapeutic index) often have their blood levels monitored. Results from therapeutic
drug monitoring assist clinicians with appropriate dosing adjustments to prevent
toxicity and achieve appropriate clinical outcomes. Pharmacokinetic parameters as
well as drug interactions may significantly impact the laboratory results and must be
integrated into the clinical assessment of the data. Similarly, for certain drugs and
drug classes, there are recommended laboratory tests that should be performed to
monitor their potential adverse effects on organ systems. Ideally, blood level
monitoring should occur after the drug has reached steady state and at a consistent
time within the dosing interval.
PATIENT-DIRECTED MONITORING AND
Often patient-directed self-monitoring is an essential component to successful
management of certain disease states such as blood pressure monitoring for
hypertension and blood glucose monitoring for diabetes mellitus. When used
appropriately, data obtained from these monitoring devices can be used by health
care providers and consumers to initiate or modify therapies accordingly.
Additional laboratory, self-monitoring tests or devices are also available for
consumers to purchase for independent testing or screening purposes at home. Some
products provide an immediate result, whereas others require submitting a completed
kit to a laboratory for analysis. Samples may be obtained from various sources,
including urine, blood, saliva, stool, or hair samples. The incidence of consumers
using these products has significantly increased and likely will continue to climb
because of increased access via the Internet as well as additional tests becoming
In the United States, some, but not all, patient-directed tests have been approved
by the US Food and Drug Administration (FDA). A current listing of approved
products is available through the FDA’s Office of In Vitro Diagnostic Device
Evaluation and Safety (OIVD) and can be accessed online at
approved and the validity of all test results, especially for diagnostic purposes,
because many factors can impact or interfere with the sensitivity (probability of
obtaining a positive result when sample is truly positive) and specificity (probability
of obtaining a negative result when the sample is truly negative). Follow-up
assessment with a health care provider should be encouraged to confirm or refute
patient-directed test results.
A full list of references for this chapter can be found at
http://thepoint.lww.com/AT11e. Below are the key references and websites for this
chapter, with the corresponding reference number in this chapter found in parentheses
Drug Information, LLC. Updated March 24, 2015. (2)
Kratz A et al, eds. Laboratory reference values. N EnglJ Med. 2004;351: 1548–1563. (1)
Mayo Medical Laboratories Mobile App. http://www.mayomedicallaboratories.com/mobile-apps/
COMPLETE REFERENCES CHAPTER 2 INTERPRETATION
Kratz A et al. Laboratory reference values. N EnglJ Med. 2004;351:1548–1563.
Drug Information, LLC. Updated March 24, 2015.
Adrogue HJ, Madias NE. Hyponatremia. N EnglJ Med. 2000;342(21):1581–1589.
Liamis G et al. A review of drug-induced hyponatremia. Am J Kid Dis 2008;52(1):144–153.
Adrogue HJ, Madias NE. Hypernatremia. N EnglJ Med. 2000;342(20):1493–1499.
Rhodes PJ et al. Evaluation of eight methods for estimating creatinine clearance in men. Clin Pharm.
Jelliffe RW. Letter: creatinine clearance: bedside estimate. Ann Intern Med. 1973;79(4):604.
Pharmacol Ther. 1981;29(4):516.
function measurement. Kidney Int. 2004;65(4):1416.
Diabetes 2015. Diabetes Care. 2015;38(Suppl 1):S8–S16.
diabetes (UKPDS 35): prospective observationalstudy. BMJ. 2000;321(7258):405.
based on a quantitative analysis. Ann Intern Med. 1986;105(2):221.
acute myocardial infarction. Am J Cardiol. 1985;55(13 pt 1):1478.
Roberts R. Where, oh where has the MB gone? N EnglJ Med. 1985;313(17):1081.
Hamm CW. New serum markers for acute myocardial infarction. N EnglJ Med. 1994;331(9):607.
monitoring value in heart failure for primary care physicians. J Am Board Fam Pract. 2003;16(4):327.
Schmid R. Bilirubin metabolism in man. N EnglJ Med. 1972;287(14):703.
Keenan WF Jr. Macrocytosis as an indicator of human disease. J Am Board Fam Pract. 1989;2(4):252.
Winkelstein A et al. White Cell Manual. 5th ed. Philadelphia, PA: FA Davis; 1998.
Malech HL, Gallin JI. Current concepts: immunology. Neutrophils in human diseases. N Engl J Med.
Cline MG et al. UCLA Conference. Monocytes and macrophages: functions and diseases. Ann Intern Med.
Beeson PB. Cancer and eosinophilia. N EnglJ Med. 1983;309(13):792.
Butterworth AE, David JR. Eosinophil function. N EnglJ Med. 1981;304(3):154.
Dombrowicz D, Capron M. Eosinophils, allergy and parasites. Curr Opin Immunol. 2001;13(6):716.
Abuelo JG. Proteinuria: diagnostic principles and procedures. Ann Intern Med. 1983;98(2):186.
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