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Neutrophils in a cytospin will look the same as in peripheral blood. The cytospin technique will accentuate the segmentation in the nucleus. Toxic vacuolation and toxic granulation will be the same as on a peripheral smear.

The next stage of the myeloid maturation sequence is the myelocyte. The cytoplasm of this cell begins to produce specific, secondary granules. If the cell is destined to be a neutrophil these secondary granules will be pink/tan and will cause the basophilic color to lighten and breakup. At the "dawn" of neutrophilia, these secondary granules are most obvious in the golgi area. As the cell matures closer to a metamyelocyte, they fill the entire cytoplasm.While the cytoplasm shifts to producing secondary granules it also looses the prominence of its primary granules. In situations where the bone marrow is stressed or forced to make neutrophils quickly, as in sepsis or during certain therapeutic injections, some of these primary granules may persist as "toxic granules".At the same time the secondary granule production begins, the nucleus is shrinking and condensing. The nucleoli close and disappear, the chromatin gets coarser/denser and more clumped, and the chromatin gets tighter darker and more compact.The very early myelocyte (red arrow) in the top image to the right still displays its immature features. While the chromatin is not as condensed as in the intermediate and late stage myelocytes in the bottom image, notice how the cytoplasm no longer has the darker basophilic color of a promyelocyte. There are clusters of neutrophil secondary granules that are changing and breaking up the solid basophilic color. Notice too, that you can no longer see any red/purple primary granules. In this cell the cytoplasm is leading the maturational dance and the nucleus is lagging.The bottom image to the right shows two myelocytes (blue arrows): one intermediate in maturity, one a bit more mature, as well as a metamyelocyte (green arrow). Notice how the size of the cell continues to shrink as the cell matures. It is apparent that both the nucleus and the cytoplasm of the metamyelocyte adjacent has decreased in size and the chromatin has condensed/clumped as the cell matured toward a metamyelocyte.

Spencer RC.: Invasive streptococc European Journal of Clinical Microbiology & Infectious Diseases. 14 Suppl. 1:S26-32, 1995. Before the introduction of antibiotics, serious infections caused by Streptococcus pyogenes (Lancefield Group A streptococci) were common. Before World War II, this bacterium was responsible for as many as 50% of postpartum deaths and was the major cause of death in patients with burns. Also common were the sequelae of streptococcal infections-rheumatic fever and post-streptococcal glomerulonephritis. With the use of penicillin, however, Streptococcus pyogenes was believed to be virtually eliminated as a pathogen. The organism was consigned to the history books, but not for long. In the mid-1980s, focal resurgences of rheumatic fever began to be reported from different areas in the USA, such as Salt Lake City, Utah. In such communities, where increases in cases of rheumatic fever had been reported, the serotypes M-1, 3, 5, 6 and 18 were isolated which, on culture, produced characteristic mucoid colonies. At the same time, reports of increases in invasive streptococcal disease began to surface in both the US and Europe. Two syndromes were described; invasive streptococcal infection, occurring in previously healthy children and adults, commonly associated with septicaemia resulting from a deep focus of infection such as bone or lung; and streptococcal toxic shock syndrome, involving a cutaneous focus, accompanied by necrotizing or bullous soft tissue changes. Septicaemia is rare in streptococcal toxic shock syndrome, but the most characteristic feature is one of rapidly progressing multi-organ failure. A high proportion of the strains of Streptococcus pyogenes associated with this condition are serotype M-1, and fatality rates approaching 50% have been reported.

Cunningham MW.: Pathogenesis of group A streptococcal infections. Clinical Microbiology Reviews. 13):470-511, 2000 Group A streptococci are model extracellular gram-positive pathogens responsible for pharyngitis, impetigo, rheumatic fever, and acute glomerulonephritis. A resurgence of invasive streptococcal diseases and rheumatic fever has appeared in outbreaks over the past 10 years, with a predominant M1 serotype as well as others identified with the outbreaks. Emm (M protein) gene sequencing has changed serotyping, and new virulence genes and new virulence regulatory networks have been defined. The emm gene superfamily has expanded to include antiphagocytic molecules and immunoglobulin-binding proteins with common structural features. At least nine superantigens have been characterized, all of which may contribute to toxic streptococcal syndrome. An emerging theme is the dichotomy between skin and throat strains in their epidemiology and genetic makeup. Eleven adhesions have been reported, and surface plasmin-binding proteins have been defined. The strong resistance of the group A streptococcus to phagocytosis is related to factor H and fibrinogen binding by M protein and to disarming complement component C5a by the C5a peptidase. Molecular mimicry appears to play a role in autoimmune mechanisms involved in rheumatic fever, while nephritis strain-associated proteins may lead to immune-mediated acute glomerulonephritis. Vaccine strategies have focused on recombinant M protein and C5a peptidase vaccines, and mucosal vaccine delivery systems are under investigation.

The presence of an increased amount of protein in a urine specimen is often the first indicator of renal disease. Proteinuria may signal severe kidney damage, be a warning of impending kidney involvement, or be transient and unrelated to the renal system. Further quantitative testing of urine for protein may be needed to determine the significance of the proteinuria. Proteinuria related to kidney impairment may be due to glomerular membrane damage caused by toxic agents, immune complexes found in lupus erythematosus, or streptococcal glomerulonephritis. The amount of protein present in urine samples from patients with glomerular damage usually ranges from 10-40 mg/dL. If the urinary protein is due to a disorder that affects tubular reabsorption, the urine protein quantities will be much greater. In patients with multiple myeloma, proteinuria is due to the excretion of the Bence Jones protein. This low molecular weight protein produced by a malignant clone of plasma cells circulates in the blood and is filtered in the kidneys in quantities exceeding the tubular capacity. This excess protein is excreted in the urine.

Proteinuria related to kidney impairment may be due to glomerular membrane damage caused by toxic agents, immune complexes found in lupus erythematosus, or streptococcal glomerulonephritis. The amount of protein present in urine samples from patients with glomerular damage usually ranges from 10-40 mg/dl. If the urinary protein is due to a disorder that affects tubular reabsorption, the urine protein quantities will be much greater. In patients with multiple myeloma, proteinuria is due to the excretion of the Bence Jones protein. This low molecular weight protein produced by a malignant clone of plasma cells circulates in the blood and is filtered in the kidneys in quantities exceeding the tubular capacity. This excess protein is excreted in the urine.

No blood is found in the urine of healthy individuals although samples from menstruating females, frequently, but not always, test positive for blood. Hematuria is associated with renal or genital urinary disorders in which the bleeding is the result of irritation to the involved organs or trauma. Examples include renal calculi, pyelonephritis, glomerulonephritis, tumors, trauma or exposure to toxic chemicals or drugs and/or strenuous exercise. Hemoglobinuria may be due to the lysis of red cells within the urinary tract. If it is caused by intravascular hemolysis, the hemoglobin is then filtered through the glomeruli. In the normal individual, the hemoglobin molecule attaches to haptoglobin and in this way bypasses the kidney filtration system. When the hemoglobin/haptoglobin system is overwhelmed, as in cases of hemolytic anemia, severe burns, transfusion reaction, infection or strenuous exercise, hemoglobin passes into the urine.

Ketonuria can also be found in conditions associated with a decreased intake of carbohydrates (starvation), digestive disturbances, dietary imbalance (high fat/low carbohydrate diet), eclampsia, prolonged vomiting and diarrhea, glycogen storage diseases, vigorous exercise, fever, and following administration of anesthesia. Ketone bodies are mildly toxic to the body, tending to interfere with the excretion of uric acid, produce mild depression of the central nervous system, and cause acidosis.

Because hereditary hemochromatosis (HH) is a disease of iron overload, a review of the basic principles of iron metabolism is helpful in understanding its pathophysiology. Iron is needed by all body cells and is crucial for oxygen transport, oxidative metabolism, and cell growth and proliferation. To serve these functions, iron must be bound to protein. Iron is potentially harmful when ionized or complexed to inorganic compounds. Iron must be present in amounts sufficient to carry out these normal functions, but not in excessive amounts which may be toxic.Two types of iron-containing compounds are normally found in the body: compounds that serve in metabolic or enzymatic functions and storage compounds. Hemoglobin, myoglobin, cytochromes and other proteins are involved in oxygen transport and utilization. Iron in hemoglobin comprises about 67% of total body iron, thus erythrocytes are rich in iron. Approximately 27% of iron is found in storage compounds. Myoglobin, other tissue iron, and transport iron comprise the remaining 6% of total body iron. (2)

Prevention of HIV exposure is the best line of defense to prevent occupational transmission of HIV as there is no vaccine available to develop specific immunity and the postexposure prophylaxis is toxic. Following appropriate workplace practices in the laboratory focus on preventing needlesticks or other sharps injuries and exposure of mucous membranes and abraded skin to HIV-infected blood or body fluids.

Chemical warfare agents are poisonous vapors, aerosols, liquids, or solids that have toxic effects on people, animals or plants. They can be released in a number of ways such as by bombs or sprayed from aircraft. Some chemical agents are odorless and tasteless. They can have an immediate effect (such as a few seconds to a few minutes), or a delayed effect (from several hours to several days). Even though chemical agents have the potential to be lethal, they are difficult to deliver in lethal concentrations, particularly in outdoor situations where they tend to dissipate rapidly.

At present, 5 laboratories participate in Level 1 activities. At this level, technical personnel are trained to detect exposure to an expanded number of chemicals in human blood and urine. This includes all Level 3 and 2 laboratory analyses, plus analyses for mustard agents, nerve agents, and other toxic chemicals.

CultureBacterial culture, utilizing selective/differential media, is an effective method for recovering Clostridium difficile. Its drawbacks are the length of time required (up to four days), as well as the inability to distinguish toxigenic strains from non-toxigenic strains. Positive cultures require follow-up testing for the ability to produce toxin.Cell Cytotoxicity Neutralization Assay (CCNA) This assay detects the presence of C. difficile toxin in fecal samples. A filtrate of stool sample is prepared and inoculated onto sensitive tissue culture cells. Typically human fibroblast cells are utilized; if toxin is present in the filtrate, it causes the fibroblasts to round up in a characteristic cytopathic effect. To verify that the cytopathic effect is caused by C. difficile toxin (and not some other toxic component or viral agent), the filtrate is also inoculated in parallel onto a second set of tissue culture cells, to which C. difficile specific anti-toxin has been added. Absence of cytopathic effect in the second set of cell cultures provides evidence that the cellular changes in the first set were caused by C. difficile toxin. Although CCNA is considered a gold standard for the detection of C. difficile toxin, it is labor intensive, requires the use of cell cultures, and requires at least 48 hours of incubation.

Staphylococci are non-motile, non-spore-forming, gram-positive organisms occurring singly, in pairs, tetrads or in clusters resembling grapes. More than 20 species have been identified; three species are significant in their interactions with humans - S. aureus, S. epidermidis and S. saprophyticus.The staphylococci are members of the normal flora of the skin and mucous membranes of humans and warm-blooded animals. Colonization of the nares (nostrils) and skin can provide large reservoirs of organisms for transmission. Approximately 25-30% of the general population are colonized by Staphylococcus aureus, mainly in the nasal passages, but the organism can be found in most anatomical sites including the skin, oral cavity and GI tract.Infections are frequently acquired when the colonizing strain gains access to a normally sterile site as a result of trauma or abrasion to skin or mucosal surface. S. aureus infections range from superficial, localized skin infections, such as folliculitis, to deeper, more serious skin lesions and the more serious toxin mediated conditions – scalded skin syndrome and toxic shock syndrome.

The Cell Cytotoxicity Neutralization Assay (CCNA) was developed to detect the presence of C. difficile toxin in fecal samples.In this assay, a filtrate of stool sample is prepared and inoculated onto sensitive tissue culture cells. Typically human fibroblast cells are utilized; if toxin is present in the filtrate, it causes the fibroblasts to round up in a characteristic cytopathic effect.To verify that the cytopathic effect is in fact caused by C. difficile toxin (and not by some other toxic component or viral agent) the filtrate is also inoculated in parallel onto a second set of tissue culture cells, to which C. difficile specific anti-toxin has been added.Absence of the cytopathic effect in the second set of cell cultures provides evidence that the cellular changes in the first set were caused by C. difficile toxin.Although CCNA is considered a gold standard for the detection of C. difficile toxin, it is labor intensive, requires the use of cell cultures, and requires at least 48 hours incubation.

Clostridium difficile is the leading cause of hospital-acquired diarrhea in the United States, with the number of cases rising annually over the last three decades. This is largely due to the increased frequency of antibiotic usage, the development of better detection methods, and the fact that hospital environments are increasingly contaminated with spores of C. difficile. The definition of C. difficile diarrhea includes > 6 episodes of non-formed diarrheic stool per 24 hours, along with prior antibiotic treatment. At least three events must occur in the pathogenesis of C. difficile-associated diarrhea (CDAD): Alteration of the normal fecal flora Colonic colonization with toxigenic C. difficile Growth of the organism with elaboration of its toxins"Colonization resistance" is the term used to describe the mechanism by which indigenous flora control overgrowth of C. difficile. This resistance may be compromised by the use of antimicrobial compounds, underlying illness, or therapeutic procedures. Infection begins with the ingestion of either the organism itself or spores, usually via the fecal-oral route. Spores in particular are able to survive the acidity of the stomach and germinate in the colon to produce vegetative organisms. Toxinogenic strains subsequently produce Toxin A, Toxin B, and/or the Binary Toxin leading to colitis, pseudomembrane formation, and watery diarrhea. Significant complications of the clinical disease associated with infection are hypoalbuminemia, toxic megacolon (acute toxic colitis with dilatation of colon), and pseudomembranous colitis (PMC).

The US Department of Transportation (DOT) classifies hazardous materials according to the risks that they pose. There are nine hazard classes: Class 1: Explosives Class 2: Gases Class 3: Flammable liquids Class 4: Flammable solids Class 5: Oxidizers/organic peroxides Class 6: Toxic and infectious substances Class 7: Radioactive material Class 8: Corrosives Class 9: Miscellaneous hazardous materials Within class 6 are two divisions: Division 6.1- poisonous material Division 6.2- infectious substanceA division 6.2 infectious substance is defined as a material known or reasonably expected to contain a pathogen. A pathogen is a microorganism or other agent (e.g., a prion) that can cause disease in humans or animals. The regulations that govern packaging and shipping a class 9, miscellaneous hazardous material, may also need to be reviewed by those who package and ship laboratory specimens. Dry ice is a class 9 hazardous material and, if used, requires special packaging, and specific labeling and marking on the outer package.

In order to discuss TDM and PGx we need to also introduce the concept of pharmacokinetics. Pharmacokinetics is the study of drug disposition in the body: how and when drugs enter the circulation, how long they remain in the blood, and how they are eliminated. TDM is the clinical assessment of a drug's pharmacokinetic properties. Physicians and pharmacists need to establish that a drug is present at an effective concentration but not at a toxic concentration. The next few pages will describe some of the factors that determine a drug's disposition in the body. These factors ultimately decide the need for therapeutic drug monitoring.

Every drug has a sub-clinical concentration (a concentration at which effective therapy won't be achieved) and a toxic concentration (a concentration at which the drug will be harmful to the patient.)For some drugs, the range between the minimum effective concentration and the toxic concentration is large. These drugs are thus relatively safe. Other drugs have a very narrow therapeutic window and need closer monitoring. This is the role of TDM.Medications with narrow therapeutic windows, like the anticonvulsant carbamazepine (Tegretol), should be closely monitored since elevated doses can cause serious conditions such as agranulocytosis.

Anthrax (B. anthracis): Inhalation of anthrax spores is virtually 100% fatal Spores can remain infectious for decadesBotulism: Most lethal toxic agent known Toxin could be used to contaminate food supplies Can be aerosolized in enclosed areasPneumonic Plague (Y. pestis): Aerosolized in large amounts Short incubation period, usually in less than three days, and invariably fatal without early and effective antimicrobial therapy Untreated, fatality rate exceeds 90% Disease is spread from direct exposure to respiratory droplets of infected humansSmallpox: Highly contagious and deliberate spread by aerosol is extremely infectious Mass panic would be createdTularemia (F. tularensis): Highly contagious and easily spread An aerosol containing as few as 25 organisms can cause infection Easily penetrates the smallest breaks in the skinViral Hemorrhagic Fever: Causes internal and external bleeding and would likely cause great panic and easily spread by direct contact with body fluids or respiratory droplets Outbreak due to bioterrorist attack could lead to mass illness and death

Other aspects of specimen collection that must be considered are the temperature of the specimen and the time needed to transport it to the laboratory.Ideally, the specimen should be collected in a room at the testing site.If onsite collection is not possible:The specimen should be kept between 20 -37°C (room temperature to body temperature) from the time of collection until it arrives at the laboratory. This can be facilitated by holding the container close to the body, for example by carrying it in an inside pocket.Semen should arrive at the laboratory as soon as possible after collection, preferably within one hour.The man should record the time of semen production.The report should note that the sample was collected at a location outside the laboratory.

In order to test collection containers for sperm collection, the sperm must be held in the container for several hours to ensure that neither the numbers nor motility are adversely affected. Numbers will decline if the sperm adhere to the container. Motility will decline if the container is toxic. One method of testing involves removing sperm from semen. The specimen would be centrifuged and the sperm pellet diluted in a small volume of culture medium containing an energy source and at least 0.5% of a protein, such as serum albumin. The processed sperm specimen would be placed in the container to be tested. Total count and motility of the sperm would be tested at the start of incubation and 24 hours later. The container is non-toxic if the motility at the end of 24 hours is no less than 50% of the original value.

Therapeutic drug monitoring helps to ensure that a dosing regimen is appropriate for a given patient. The blood plasma concentration of the drug is measured to determine the correct dose that will achieve a therapeutic level of the drug without overdosing into a toxic range. When a drug enters the body, it reaches a peak concentration that starts to fall as the drug is eliminated.The amount of time it takes for a drug's concentration in the body to decrease by 50% is called the drug's half-life. The longer a drug's half-life, the slower it is removed from the body. Most drugs are eliminated from the body in one to three days, but some drugs with longer half-lives can still be detected in the body weeks after the initial dose.The figure on the right illustrates a typical concentration pattern for a drug that is given orally (ingested).

Vacuoles are frequently seen in conditions such as infection or burns when toxic granulation is also present. The cell in this image exhibits toxic vacuolation as well as toxic granulation. Note: Toxic vacuolation and toxic granulation are classified as reactive and not pathologic since the body is responding normally in an effort to rid itself of infection caused by bacteria.

Toxic granulation is present in the neutrophil in this image.

Toxic granulation is manifested by the presence of large granules in the cytoplasm of segmented and band neutrophils in the peripheral blood. The color of these granules can range from dark purplish blue to an almost red appearance. Toxic granules are actually azurophilic granules, normally present in early myeloid forms, but are not normally seen at the band and segmented stages of neutrophil maturation. These granules contain peroxidases and hydrolases. Toxic granulation is seen in cases of severe infection, as a result of denatured proteins in rheumatoid arthritis or, less frequently, as a result of autophagocytosis. Infection is the most frequent cause of toxic granulation. This phenomenon may be seen in cells which also contain Döhle bodies and/or vacuoles. Cells containing toxic granules may have decreased numbers of specific granules. Note: Cells containing only a few specific granules, with or without toxic granules, are said to be degranulated. The nucleus in degranulated cells may often be round-bilobed, smooth and pyknotic. This type of nucleus is the result of aging and will disintegrate soon. Increased basophilia of azurophilic granules simulating toxic granules may occur in normal cells with prolonged staining time or decreased pH of the stain. The blue arrow in the image points to a neutrophil with toxic granulation. Döhle bodies are also present in the cell, indicated by the red arrows.

This image shows a band neutrophil with toxic granulation. The granules scattered throughout the cytoplasm are larger, more numerous and darker than those of normal neutrophils.

An example of a normal neutrophil, lower left, and one showing some increased granulation, typical of that seen in Alder-Reilly anomaly. Morphologically, it may be difficult to distinguish these granules from toxic granulation; however, the diagnosis is made on the basis of the presence of the many distinctive physical characteristics.

Alder anomaly is a rare autosomal recessive disorder in which the basic defect involves protein-carbohydrate complexes called mucopolysaccharides. The accumulation of partially degraded (broken down) protein-carbohydrate complexes within the lysosomes account for the larger than normal purple-staining inclusions seen in all types of mature white blood cells, and sometimes in earlier cells. The granules may occur in clusters, rather than diffusely, throughout the cytoplasm as in toxic granulation. These inclusions may be seen in the bone marrow more frequently than in peripheral blood. The physical characteristics associated with this disorder include gargoylism and dwarfism. The function of the cells involved is not affected. This morpholical change would be classified as pathological since the body is responding abnormally even though the function is not affected.

Several additional familial and congenital disorders associated with atypical inclusions in WBCs are now recorded. These individual syndromes carry the following names: Fechtner, Alport, Epstein, Sebastian, and Paris-Trousseau.Fechtner syndrome( Peterson etal,Blood 65:397-406,1985)was described with 8 family members spanning 4 generations presenting with varying degrees of nephritis, deafness,and congenital cataracts. The syndrome is likely a variant of Alport syndrome with the addition of leukocyte inclusions and macrocytothemia. Several more cases involving other families have been reported. The inclusions resemble toxic Doehle bodies or those of the May-Hegglin anomaly by light microscopy, but are ultrastructurally unique.Alport syndrome is autosomal dominant, X-linked , hereditary and characterized by sensorineural deafness and hereditary nephritis. It is believed to result from abnormal glycopeptide synthesis in renal basement membranes. Recurrent hematuria and slowly progressive renal insufficiency are clinical findings. Cataracts and platelet abnormalities may be added features.Epstein syndrome is essentially Alport syndrome with the addition of macrothrombocytopenia (Seri, et al. Hum Genet 110:182-186, 2002). Neutrophil inclusions are absent in this disorder; neutrophilic inclusions are considered part of the Fechtner syndrome.The Sebastian platelet syndrome is a variant of hereditary macrothrombocytopenia combined with neutrophil inclusions that differ from Doehle bodies, but are similar to those inclusions in Fechtner syndrome. (Greinacher, et al, Blut 61:282-288, 1990).Paris-Trousseau syndrome includes large platelets containing giant alpha granules identifiable in the peripheral blood.(Breton-Gorius, Blood 85:1805,1995)

The presence of atypical inclusions within the cytoplasm of neutrophils and other leukocytes should lead to a clinical investigation of the setting for these findings. Atypical neutrophil inclusions may be seen in the following disorders: Chediak-Higashi syndrome, May-Hegglin anomaly, Alder-Reilly anomaly, Fechtner , Sebastian, Epstein and Alport-like syndromes and in infectious and toxic conditions (in the form of Dohle bodies).Although a specific entity may not be evident from examination of the peripheral blood alone, it is important that hematology technologists include a comment reporting on the presence of these inclusions or granules. A clinical investigation with further hematologic and genetic studies may then appropriately be considered. Many of the disorders with atypical neutrophil cytoplasmic granules are also associated with platelet abnormalities, particularly giant platelets (lower image). Therefore, when atypical granules are recognized, scanning of the peripheral blood smear for atypical platelets may be revealing. These observations serve as readily identifiable markers for acquired and genetic human maladies, and as a guide for unraveling the reasons for a patient's suffering and impaired health.

May-Hegglin anomaly is an inherited dominant condition in which large (2 - 5 um) basophilic inclusions, resembling Döhle bodies, are present in granulocytes, including neutrophils, eosinophils, basophils, and monocytes. The inclusions are caused by accumulation of free ribosomes. A May-Hegglin body is indicated by the black arrow in the image on the right. Note that this inclusion is well-defined and there is no evidence of toxic granulation in the cytoplasm. When Döhle-like bodies are identified, May-Hegglin anomaly should be considered in the differential diagnosis, even though this entity is rare. Giant platelets containing few fine granules are also characteristic of May-Hegglin anomaly. The red arrow in the image on the right points to a giant platelet, observed in the same field as a neutrophil containing a May-Hegglin body. Sometimes the platelets have bizarre shapes and variable sizes. Variable degrees of thrombocytopenia complicated by mild bleeding problems and purpura may accompany the aberrant platelets.

An 80-year-old man was seen in the emergency room with sudden onset of right-side chest pain accentuated on inspiration. His cough was productive of yellow sputum, and he was short of breath. His temperature was 101.2°F. A chest X-ray revealed right middle lobe pneumonia. A complete blood count (CBC) was ordered. The results were as follows:CBC ParameterPatient ResultReference IntervalWBC33.0 x 109/L4.0 - 11.0 x 109/LRBC4.5 x 1012/L4.5 - 5.9 x 1012/LHemoglobin15.2 g/dL13.5 - 17.5 g/dLHematocrit44%41 - 53%Platelet200 x 109/L150 - 450 x 109/LSegmented neutrophil6540 - 80%Band neutrophil100 - 5%Lymphocyte 525 - 35%Eosinophil 30 - 5%Basophil 20 - 2%Monocyte252 - 10%A peripheral smear was reviewed based on the elevated WBC and increased monocyte count. A representative field from the Wright-Giemsa stained smear (1000X magnification) is shown on the right. The cells indicated by the blue arrows are atypical monocytes. They have abundant cytoplasm that is more blue than the typical gray-blue cytoplasm of normal monoctes. A few scattered vacuoles are also present. The atypical monocytes, in company with toxic neutrophils (indicated by the red arrow), appeared to be a response to infection. The patient had a past history of tuberculosis, which may account for the monocytosis.