Abnormalities Information and Courses from MediaLab, Inc.

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Cerebrospinal Fluid
Abnormalities Many of the samples received may have one or more of the following abnormalities: turbidityfibrinogen clot/pelliclebloody appearancexanthochromia	View Page
Macroscopic abnormalities may include which of the following?	View Page

Erythrocyte Inclusions - Wright Stained Smears
What abnormalities can be seen in this slide?	View Page
There are no abnormalities in this slide.	View Page
What abnormalities are present in this slide?	View Page

Fundamentals of Hemostasis
Laboratory Tests of Hemostatic Function – Prothrombin Time The prothrombin time is a screening test that helps to assess the functionality of both the extrinsic and common pathways. The effectiveness and presence of factors I, II, V, VII, and X are assayed in this diagnostic test, as they are all found in the aforementioned pathways. The results of the prothrombin time are used in conjunction with other diagnostic tests, as well as the clinical picture of the patient, to determine any hemostatic abnormalities which may be present. In addition to being an integral part of the coagulation disorder assessment process, the PT is also used to determine therapeutic effectiveness of oral anticoagulants, by monitoring drugs such as Warfarin, Coumarin, and Dicoumarol. Prothrombin time test results are reported as the number of seconds needed for a clot to form in the patient specimen using the laboratory's instrument/reagent system, and as the International Normalized Ratio (INR).	View Page
Laboratory Tests of Hemostatic Function - APTT The activated partial thromboplastin time (APTT) is a screening test that helps to assess the functionality of both the intrinsic and common pathways. The effectiveness and presence of all the coagulation factors are assayed by this diagnostic test with the exception of factors VII and XIII. The results of the activated partial thromboplastin time are used in conjunction with other diagnostic tests, as well as the clinical picture of the patient, to determine hemostatic abnormalities which may be present. In addition to being an integral part of the coagulation disorder assessment process, the APTT is used to determine therapeutic effectiveness of heparin administration. Activated partial thromboplastin time results are presented to the clinician in seconds- the actual time elapsed until a clot was detected using the laboratory's instrument/reagent system.	View Page

Laws and Rules of the Florida Board of Clinical Laboratory Personnel

Description of Specialties (4)

Specialists in cytogenetics detect chromosome abnormalities and genetic disorders. Cytogenetics counseling may only be performed by an individual licenses in the cytogenetics specialty at the director level. Specialists in molecular genetics analyze DNA and RNA to find disease-related genotypes, mutations, and phenotypes in order to detect or predict disease and identify carriers. Specialists in histocompatibility test to determine tissue compatibility, prevent infections, and investigate and post-transplant problems. Techniques include blood typing, HLA typing, HLA antibody screening, disease markers, flow cytometry, crossmatching, HLA antibody identification, lymphocyte immunophenotyping, immunosuppressive drug assays, allogenic, isogeneic and autologous bone marrow processing and storage, mixed lymphocyte culture, stem cell culture, cell mediated assays, and assays for the presence of cytokines. Specialists in andrology and embryology examine gametes and embryos, including production, morphology, number, and motility, to address issues of fertility and infertility.

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Mycology: Yeasts and Dimorphic Pathogens
The growth of the yeast-like colonies shown in the upper image was obtained on blood agar from a skin culture only in the area overlaid by virgin olive oil. The lower image is a photomicrograph of a lactophenol blue mount made from a portion of the colony. The disease associated with this fungus is:	View Page

Pharmacology in the Clinical Lab: Therapeutic Drug Monitoring and Pharmacogenomics

Enzyme Abnormalities and Drugs

The following is a list of enzymes for which known mutations have been associated with clinical effects. Enzymes Substrates (Drugs) Acetylaldehyde dehydrogenase Alcohol Acetylcholinesterase Succinylcholine Alcohol dehydrogenase Alcohol Dihydropyrimidine dehydrogenase Fluorouracil CYP2C9 Warfarin, phenytoin, losartan CYP2C19 Diazepam, omeprazole (Prilosec) CYP2D6 Many antidepressants, opioids, antiarrhythmics Glucose-6-phosphate dehydrogenase Aspirin, quinidine N-acetyltransferase Procainamide, isoniazid Thioprine methyltransferase 6-mercaptopurine UDP-glucuronosyl transferase Acetaminophen, tolbutamide, irinotecan

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Red Cell Disorders: Peripheral Blood Clues to Nonneoplastic Conditions
Reporting of laboratory data in regard to blood cell abnormalities Laboratory data must be presented to clinicians in a user friendly way to promote effective decision making. Databases must be designed to provide clear information that leads quickly to the best patient care outcome. We continue learning how to collect and retrieve laboratory data from our machines, but we are not always in tune to how entry and retrieval of data is geared to and, more directly, influences patient care outcomes. Examples of blood cell abnormalities on a peripheral blood smear that may immediately direct the physician to a specific diagnosis are: (1) presence of target cells as found in thalassemia or hemoglobinopathies and target cells in liver disease, particularly with obstructive jaundice; (2) burr cells as a signal of chronic renal disease and uremia; and (3)atypical neutrophil inclusions relating to genetic disorders. Critical appraisal of such observations could add valuable clues for a diagnosis. Laboratory professionals must establish a set of principles for orderly observation of blood cell morphology, have a clear vision of the applications of their work, and understand the potential clinical implications of their reports and interpretations. Emphasis on values and relevance focuses on patient care outcomes and their dependency on prompt availability of results and contextual interpretations.	View Page
Criteria for peripheral blood smear review Initial analysis of the peripheral blood picture is made in most clinical laboratories with an automated instrument. Samples are selected for further analysis when quantitative or qualitative abnormalities beyond a defined standard are found. The following are examples of quantitative RBC abnormalities that may prompt a blood smear review. Each laboratory, however, should develop its own guidelines: Hgb: < 8 or >18 g/dL (<10 or > 21g/dL in a newborn)Hct: <20% or > 60% in adults (<40% or >65% in a newborn)MCHC: <29 g/dLMCV: <69 femtoliters (fl) or >110flFlags generated by the hematology analyzer that indicate possible red cell abnormalities or spurious resultsAny of these findings should be followed up with a peripheral blood smear review.	View Page
Guidelines for standard reports In a study on the reporting of red blood cell morphology abnormalities conducted in Ontario, Canada (Hookey L, Dexter D, Lee DH, Laboratory Hematology 7:83-88, 2001), fewer than 50% of 33 participants used the same term to describe the quantitative frequency of peripheral blood abnormalities. Seven blood smears, each containing one of several abnormal erythrocytes-- schistocytes, teardrop cells, acanthocytes, and Howell-Jolly bodies--were evaluated by 32 participants. The participants were asked to document their evaluations from a list of quantitative terms. There was a heterogeneity in the use of terms "rare," "slight," "occasional," "few," "mild", "present," "moderate," "many," and "marked." Choices of terms were subjective without points of reference. Guidelines for establishing standardized qualitative estimations of abnormal erythrocytes in the peripheral smear are presented as follows: 1+ = 2 - 4/Oil Immersion Field (OIF) 2+ = 5 - 7/OIF 3+ = 8 - 10/OIF 4+ = >10/OIF. The terms "few," "moderate," "many," and "marked" may be substituted for the 1+ - 4+ grading system, but only when their specific points of reference are universally understood in tandem with the above guidelines. A comment should be triggered if any erythrocyte abnormalities are seen in numbers >3/OIF including, but not limited to, polychromasia, basophilic stippling, nucleated RBC's, and Howell-Jolly bodies. Rouleaux or RBC agglutination are important findings and must be documented.	View Page
Howell -Jolly bodies/ other erythrocyte environmental alterations Several erythrocyte abnormalities are present in both the upper and lower photomicrographs. Many of these atypical cells are probably present as a result of the patient's splenectomy. Considerable anisocytosis and poikilocytosis with many tear-drop cells, bite cells, fragmented forms, and a few target cells are apparent. Some of the erythrocytes in the upper frame contain Howell-Jolly bodies (DNA fragments) that may be single or multiple, especially in myeloproliferative disorders. These inclusions stain negatively for iron and are eccentrically placed in the red cell cytoplasm. .	View Page

Red Cell Morphology
Red Cell Morphology Red cell morphology can be defined as the appearance of the erythrocytes on a Wright's stained smear.Careful examination of the red cells for the purpose of identifying abnormalities is part of the differential procedure. This examination is important because it may provide valuable diagnostic information to the physician, as well as provide a quality control mechanism to verify red cell indices values as determined by automated or manual methods.Evaluating red cell morphology involves differentiating normal morphology from abnormal and artificial morphology. The abnormal morphology covered in this unit may be seen in a variety of disorders.	View Page
Abnormal Red Cells Examples of several types of abnormal red cell forms are seen in this slide. Each of these abnormalities will be discussed in other exercises in this unit.	View Page
Size Variation Red blood cells can vary in size (diameter/volume) from smaller than normal, microcytes, to larger than normal, macrocytes. When red cells of normal size, microcytes and macrocytes are present in the same field, the term anisocytosis is used.Since the purpose of this unit is to acquaint you with the appearance (identification) of abnormal red cell morphology, percentages of abnormalities present will not be considered. It is important to be aware that rating red cell morphology for the purpose of reporting it is a skill which must be learned before you are able to complete this aspect of a differential count.	View Page

Semen Analysis
Abnormal forms There are a number of abnormalities of sperm morphology. Abnormal heads can include enlarged head, double head, round head, constricted head, amorphous head, pinhead, and acute tapering forms. There are also heads with abnormal numbers of vacuoles. Midpiece abnormalities include distended and thin midpiece regions. Abnormal tails include short tails, double, triple or multiple tails, coiled tails, broken tails, or absent tail. Cytoplasmic droplets are also seen in some specimens. These are large regions of cytoplasm just below the head assumed to represent failure of complete sperm maturation or a sign of either toxicity or oxidation. There have also been reports that cytoplasmic droplets may be artifacts from the fixation and staining for morphology analysis.	View Page
Two abnormalities The sperm in the center of the field is a pinhead. The sperm in the lower right has an amorphous head. The sperm in the upper right has a slightly enlarged head but a good acrosome.	View Page
Summary of macroscopic evaluation In summary, the macroscopic examination of semen can provide important information. Changes in semen liquefaction parameters, viscosity, volume, pH may provide clues to the clinician about causes of infertility or abnormalities of the reproductive tract.	View Page

The Urine Microscopic: Microscopic Analysis of Urine Sediment
Specimen #4 - Adult Male The results of this specimen are abnormal but the abnormalities correlate with each other. The turbidity can be explained by the presence of bacteria and crystals. The presence of RBCs in the microscopic explains the blood found on the dipstick. The casts, bacteria and WBCs can account for the increased protein. The results may be reported.	View Page

Variations in White Cell Morphology - Granulocytes

Variations in Morphology

Many variations in morphology may be seen when examining Wright's stained peripheral blood smears. One method of classifying these variations in white cell morphology is based on the way the body responds to a stimulus, deficiency, or the presence of an inherited defect. This classification falls into three groups:Pathological: Cells may show abnormalities in appearance and/or function. The body is responding abnormally to a stimulus or inherited defect, resulting in physiological impairment in the patient. Nonpathological: Cells may show variation in morphology but their function is normal. Their presence does not cause physiological impairment. Reactive: Cells show variation in morphology but are functioning normally in response to a specific stimulus, such as a virus or bacteria. There is a disease process in progress to which the cells are responding. Although the morphology has varied from normal and their presence is significant, the body is responding normally to a stimulus.

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White Cell and Platelet Disorders: Peripheral Blood Clues to Nonneoplastic Conditions
Additional comments on this exercise The following pages in this presentation includes a series of white blood cell abnormalities that may be identified in a peripheral blood smear. Many of the cases will simulate the practice of a peripheral smear review by a hematology morphologist. He/she must asses what responses in patient care may be triggered by the clinician attempting to interpret the reported findings on a peripheral smearObservations of white blood cell abnormalities in the peripheral blood smear should be reported so as to direct the physician to an immediate specific diagnosis, such as: (1) atypical lymphocytes suggesting infectious mononucleosis rather than leukemia, (2) toxic granules in neutrophils as in acute infections, or atypical granules suggesting a genetic disorder, (3) an unusual mix of cells, such as too many or too few neutrophils, monocytes, or other myeloid cells, and (4) the presence of giant platelets, myelocytes, or other cells suggesting a myelodysplastic syndrome.In summary, laboratory data should be presented to clinicians in a user friendly way to promote effective decision making. The design of the data base of information must be directed toward providing clinically helpful information clearly and quickly in order to facilitate appropriate action in terms of optimizing patient care outcomes.d	View Page
Familial disorders: summary 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 in itself 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)	View Page
WBC inclusions: summary 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 Doehle 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 photograph).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.	View Page