Solution Manual for Clinical Laboratory Hematology, 2nd Edition

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Resource ManualLinda F. Comeaux, BS, CLS(NCA)Dean, Health, Sciences, and EngineeringArapahoe Community Collegeto AccompanyClinical Laboratory HematologySecond EditionShirlyn B. McKenzie, PhD, CLS(NCA), MT(ASCP)SHDepartment of Clinical Laboratory SciencesUniversity of Texas Health Science Center at San AntonioJ. Lynne Williams, PhD, CLS(NCA), MT(ASCP)Medical Laboratory Sciences ProgramOakland University

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CONTENTSIntroduction11Introduction to Hematology202The Hematopoietic System333The Anemias494Nonmalignant Disorders of Leukocytes825Neoplastic Hematologic Disorders976Body Fluids1177Hemostasis1298Hematology/Hemostasis Procedures147Appendix169Laboratory Worksheet—Differential Worksheet170Laboratory Worksheet—Blood Smear Evaluation171Answers to Practice Questions172iii

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201Introduction to HematologyA.TRANSITION GRIDInformation concerning Chapter 1, “Introduction; ” Chapter 2, “Cellular Homeostasis;” and Chapter3, “Hematopoiesis” may also be referenced in the following hematology textbooks.Clinical Laboratory HematologyChapter 1Chapter 2Chapter 3McKenzie, 1st editionChapter 1Chapter 2Chapter 2Harmening, 5th editionn/an/aChapter 1Rodak, 3rd editionn/aChapter 6Chapter 7Turgeon, 4th editionn/aChapter 3Chapter 4B.OBJECTIVESChapter 1 – IntroductionLevels I and II1. Compare the reference intervals for hemoglobin, hematocrit, erythrocytes, and leukocytes in in-fants, children, and adults.2. Identify the function of erythrocytes, leukocytes, and platelets.3. Describe the composition of blood.4. Explain the causes of change in the steady state of blood components.5. Describe clinical pathway, critical pathway, reflex testing, and disease management and identifythe laboratory’s role in developing these models.6. Compare capitated payment, prospective payment, and fee-for-service and describe the impactof capitation on the laboratory.

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1Introduction to Hematology21Chapter 2 – Cellular HomeostasisLevel I1. Describe the location, morphology, and function of subcellular organelles of a cell.2. Describe the lipid asymmetry found in the plasma membrane of most hematopoietic cells.3. Differentiate the parts of the mammalian cell cycle.4. Define R (restriction point) and its role in cell cycle regulation.5. Defineapoptosisand explain its role in normal human physiology.6. Classify and give examples of the major categories of initiators and inhibitors of apoptosis.7. List the major events regulated by apoptosis in hematopoiesis.Level II1. Explain the significance of SNPs, introns, exons, UTRs, post-translational protein modifications.2. List the components and explain the function of the Ubiquitin-Proteosome system.3. DefinecyclinsandCdksand their role in cell cycle regulation; describe the associated Cdk partnersand function of cyclins D, E, A, and B.4. DefineCAK(Cdk-activating kinase) and the two major classes of CKIs (cyclin-dependent kinaseinhibitors) and describe their function.5. Compare the function of cell-cycle checkpoints in cell-cycle regulation.6. Describe/illustrate the roles of p53 and pRb in cell-cycle regulation.7. Propose how abnormalities of cell-cycle regulatory mechanisms can lead to malignancy.8. Definecaspasesand explain their role in apoptosis.9. Differentiate the extrinsic and intrinsic pathways of cellular apoptosis.10. Define and contrast the roles of proapoptotic and antiapoptotic members of the Bcl-2 family ofproteins.11. Describe apoptotic regulatory mechanisms.12. Give examples of diseases associated with increased apoptosis and inhibited (decreased)apoptosis.13. Define, and give examples of, epigenetics, oncogenes and tumor suppressor genes and theirroles in cell biology.14. Differentiate using morphologic observations, the processes of necrotic cell death and apoptoticcell death.Chapter 3 – HematopoiesisLevel I1. Describe the basic concepts of cell differentiation and maturation.2. Compare and contrast the categories of hematopoietic precursor cells: hematopoietic stem cells,hematopoietic progenitor cells, and maturing cells, including proliferation and differentiationpotential, morphology, and population size.3. Describe the hierarchy of hematopoietic precursor cells and the relationships of the variousblood cell lineages to each other (including the concept of colony-forming units/CFUs).

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224. Discuss the general characteristics of growth factors and identify the major examples of earlyacting (multilineage), later acting (lineage restricted), and indirect acting growth factors.5. Differentiate between paracrine, autocrine, and juxtacrine regulation.6. List examples of negative regulators of hematopoiesis.7. Definehematopoietic microenvironment.Level II1. Identify the phenotypic characteristics differentiating the hematopoietic stem cells and progenitorcells.2. Identify the key cytokines required for lineage-specific regulation.3. Describe the structure and role of growth factor receptors.4. Summarize the concept of signal transduction pathways.5. Discuss the roles of transcription factors in the regulation of hematopoiesis and differentiation.6. Outline current clinical uses of cytokines.7. Describe the cellular and extracellular components of the hematopoietic microenvironment.8. Discuss the proposed mechanisms used to regulate hematopoietic stem/progenitor cellproliferation/differentiation.Note:Statements in parts C, D, & E identified with asterisks suggest Level II competenciesC.ACTIVE LEARNING SUGGESTED ACTIVITIES{Background information on each suggested activity is provided in theIntroduction/Teaching Tipssection atthe beginning of this.}1.Clear the MudAt the end of class, pass out index cards to all students and ask each of them towrite down any topic, current or past, that is still unclear. Have students place their respectiveindex cards into a container on the instructor’s desk. As students leaves, they should randomlypick an index card from the container, research the topic, and prepare an answer or explanationto the “muddy point” written on the card. The instructor may choose to ask a few students topresent their explanation during the next class period.2.Diagramsa. Using the information provided in Chapter 2, have the learners create their own explicit dia-gram of the:• Cell structure• Stages of the cell cycle•Hematopoietic precursor cell model3.Group Discussiona. Create a group discussion on the topic of the Medical Ethics concerning stem cell transplants.4.Mystery Boxa. Create a Mystery Box with the different blood components and corresponding referenceranges. Be sure to include at least• Leukocytes• Erythrocytes**

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1Introduction to Hematology23• Thrombocytes• Plasma• Whole blood•••• 55 percent of blood volume• 5 – 6 liters in adults• And so on5.One-Minute ParagraphHave learners submit a one minute paragraph on the:a. Composition of bloodb.Abnormal tissue homeostasis and cancer6.Short StoryHave the learners, individually or as a group, write:a. The story of “The Life and Development of a Cell”b. A “Murder Mystery” of a Cell7.Think-Pair-Sharea.Discuss the value and need for “clinical” and “critical” pathways.b.Discuss Necrosis versus Apoptosis.8.Thumbs Up/Thumbs DownRemember to get immediate feedback on any topic during theclass period, call for a quick “Thumbs Up or Thumbs Down.” Ask students to indicate if theycomprehend the information presented by showing either a thumbs up, indicating they un-derstand the information, or thumbs down, meaning more explanation or clarification isneeded.D.LABORATORY ACTIVITIES1.Perform WBC and RBC counts on each learner in the class, and create a “class reference range”for WBC and RBC. You might want to have students read the section “Reference Interval Deter-mination” in Chapter 41 if you include this activity.E.PRACTICE QUESTIONS1. List the components of whole blood and state the reference range for each. [Taxonomy 1]2.Explain why “reflex testing protocols” are designed. [Taxonomy 1].3. A patient experiencing a viral infection is likely to demonstrate an increase in which of the fol-lowing? [Taxonomy 1]a. Erythrocytesb. Hematocritc. Leukocytesd. Thrombocytes4. Patient Aaron had an RBC count ofExplain why a hospital in Alabama might con-sider this value “normal,” whereas a facility in Utah may recognize Aaron’s RBC as “below”normal. [Taxonomy 2]5.In the textClinical Laboratory Hematology,differentiate “precursor cells” from “maturing cells.”[Taxonomy 2]**4.0*1012/L.**********150-450*109/L4.5-5.5*1012/L4.5-11.0*109/L

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24Which set of results demonstrates aa. Leukocytosisb. Erythrocytopeniac. Thrombocytopeniad. Critically decreased H & He. Leukopeniaf. Thrombocytosis7.Compare and contrast a “fee-for-service” reimbursement system to a “capitated payment” plan.[Taxonomy 3]8. Compare and contrast the processes of cell “self-renewal” versus “cell differentiation.” [Taxonomy 3]9. Evaluate the following patient results and conclude which body function (mechanism) will beadversely affected. Explain why. [Taxonomy 3]10. A 26-year-old male, Type I diabetes mellitus patient is seen in the emergency department. Thepatient’s blood chemistry results confirm the need for renal dialysis. Explain the etiology for thispatient’s hematology results. [Taxonomy 3]Plt=321*109/LHct=27.6%Hgb=9.5 g/dLRBC=3.2*1012/LWBC=11.8*109/LPlt=222*109/LHct=25.1%Hgb=8.2 g/dLRBC=2.5*1012/LWBC=0.8*109/L**A.B.C.WBC=18.6*109/LWBC=0.6*109/LWBC=6.5*109/LRBC=3.50*1012/LRBC=2.12*1012/LRBC=4.79*1012/LHgb=10.2 g/dLHgb=7.5 g/dLHgb=16.4 g/dLHct=31.1%Hct=24.3%Hct=49.6%Plt=202*109/LPlt=89*109/LPlt=543*109/L6. Analyze each set of results and answer the following questions. [Taxonomy 2]

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1Introduction to Hematology25VHEHNJNHDTRFNEMMNLPSCTDTSSSZTXESOYYREYLTEEMYSNMIIHRGYDENNHCNUMBSTRECYMEIKOBKEMROAPVMCGKPBLNLLNATRRHEOOGMAQBNCMNPEZLCTSOSWIXTUMEOFLNYLRTPQRDLNHWPIOCTHEMATOLOGYTALQTTXPLZSXQLCWMMOKKYZTVRDIXYVWFLRDGGGLVTNPSMRWYVPQLFEUCHROMATINDRNNRMKCNALBUMINCLSISEIOPOTAMEHMWIntroduction to Hematology—Level I• cell division—repeated reproduction• another term for hematopoietic growth factor• study of formed cellular blood elements• process of forming a blood clot• outer boundary of a cell• the earliest morphologically recognizable cell of each blood cell lineage• the process of blood cell formation• how a blood cell passes through vessel walls• part of cell that contains the genetic material• genes that induce tumor formation• main constituent of plasma• programmed cell death• platelet• lightly stained portions of chromatin• undifferentiated, pleuripotential hematopoietic cell (2 words)Figure out what words the clues represent. Then find the words in the grid. Words can go horizontally, vertically, anddiagonally in all eight directions.

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26VHEHNJNHDTRFNEMMNLPSCTDTSSSZTXESOYYREYLTEEMYSNMIIHRGYDENNHCNUMBSTRECYMEIKOBKEMROAPVMCGKPBLNLLNATRRHEOOGMAQBNCMNPEZLCTSOSWIXTUMEOFLNYLRTPQRDLNHWPIOCTHEMATOLOGYTALQTTXPLZSXQLCWMMOKKYZTVRDIXYVWFLRDGGGLVTNPSMRWYVPQLFEUCHROMATINDRNNRMKCNALBUMINCLSISEIOPOTAMEHMWIntroduction to Hematology—Level I• cell division—repeated reproduction (proliferation)• another term for hematopoietic growth factor (cytokines)• study of formed cellular blood elements (hematology)• process of forming a blood clot (hemostasis)• outer boundary of a cell (membrane)• the earliest morphologically recognizable cell of each blood cell lineage (blast)• the process of blood cell formation (hematopoiesis)• how a blood cell passes through vessel walls (diapedese)• part of cell that contains the genetic material (nucleus)• genes that induce tumor formation (oncogenes)• main constituent of plasma (albumin)• programmed cell death (apoptosis)• platelet (thrombocyte)• lightly stained portions of chromatin (euchromatin)• undifferentiated, pleuripotential hematopoietic cell (2 words) (stem cell)

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1Introduction to Hematology27123456789101112131415ACROSS1Growth and development of lymphoid cells4Stage during which microtubular spindles alignduring mitosis7Cells that defend against foreign antigens8Where the metabolic activities of the cell takesplace12Alternate copies (alleles) of a gene13Type of cell that differentiates into mature,functional cells15Cell murderDOWN2Outside of cell3Study of the entire genome of an organism5Arrest of bleeding6Study of the formed cellular blood elements9Vital protein inside erythrocytes10Organelles that assemble amino acids intoprotein11Group of proteins responsible for apoptotic celldeath14Complete blood count (abrv)Introduction to Hematology—Level I

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28LPOIOMYHPSESIGXEMSAEATHPHHNRLUEETSOKYCOAMMMCOAIESTYPOCCALMSHTOSLEALRUMSOICLOIGBAAGYLOMOPMSPRIHLSPOEGINPORAOTRBCMSIBEEENRCSOSISSIntroduction to Hematology—Level I

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1Introduction to Hematology29LXZBKRDLNSDIPILSNEFQLIHQTRTEGCSCBLZNFNSLNNEATEWFTFXFVRCEMSFNNGBWKEERNGGPATTICBLRCRNOWABHAIKLBVVTECPSWBPDROXRMHNNWEWLOOQCTPRMIOTSWTPHRKOYMCLIYIKBTCTPNTCTCTQGAPOEPOYNAFYNNKFTSNDMKLJMCABCAPITATEDNTEKLLMHSOFHHJTTKHNXNFXTNLTYFMBLJIntroduction to Hematology—Level II• stage in mitosis where cells condense their chromosomes• tumor suppressor gene• payment plan whereby the provider is reimbursed a fixed amount for a service• growth factor that promotes proliferation and differentiation of progenitor cells (abrv)• process for generating diverse cell populations• programmed cell death• cell membranes are composed of proteins and ______• packed red cell volume• testing done based on results of screening tests• regulatory subunit of Cdks• proteins that direct apoptosis• hematopoietic growth factors• hematopoietic growth factor for erythroid cells (abrv)• precursor of all hematopoietic cells (abrv)Figure out what words the clues represent. Then find the words in the grid. Words can go horizontally, vertically, anddiagonally in all eight directions.

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30LXZBKRDLNSDIPILSNEFQLIHQTRTEGCSCBLZNFNSLNNEATEWFTFXFVRCEMSFNNGBWKEERNGGPATTICBLRCRNOWABHAIKLBVVTECPSWBPDROXRMHNNWEWLOOQCTPRMIOTSWTPHRKOYMCLIYIKBTCTPNTCTCTQGAPOEPOYNAFYNNKFTSNDMKLJMCABCAPITATEDNTEKLLMHSOFHHJTTKHNXNFXTNLTYFMBLJIntroduction to Hematology—Level II• stage in mitosis where cells condense their chromosomes (prophase)• tumor suppressor gene (antioncogene)• payment plan whereby the provider is reimbursed a fixed amount for a service (capitated)• growth factor that promotes proliferation and differentiation of progenitor cells (abrv) (scf)• process for generating diverse cell populations (differentiation)• programmed cell death (apoptosis)• cell membranes are composed of proteins and ______ (lipids)• packed red cell volume (hematocrit)• testing done based on results of screening tests (reflex)• regulatory subunit of Cdks (cyclin)• proteins that direct apoptosis (caspases)• hematopoietic growth factors (cytokines)• hematopoietic growth factor for erythroid cells (abrv) (epo)• precursor of all hematopoietic cells (abrv) (hsc)

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1Introduction to Hematology311324657891011121314ACROSS4Type of cells that differentiate into mature,functional cells5Multiprogenitor cell capable of differentiatinginto leukocytes, erythrocytes, and megakaryo-cytes (2 abrv)6Gene that can transform cells into malignantcells8Physical manifestation of an individual’sgenotype12Describes a cell that has exited the cellcycle—nonproliferative state13Specialized type of paracrine signaling—cytokine is not secreted by the cell thatproduced it14ThrombocytesDOWN1Lineage specific marker for erythrocytes2Cells of the bone marrow that include adipo-cytes, endothelial cells, and fibroblasts3Process of producing granulocytes4Describes characteristic in which growthfactors act on more than one cell type7Platelets are derived from _________9“On top of genetics”10Fat cell11Small polypeptide that tags molecules fordestructionIntroduction to Hematology—Level II

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32GGSLEGINPORROTRYLARCUFEGMMEGENNOOCOMIUMPEHEPONYTLAHPGTOLOIARPARGKOOUDIEAPIBINNRIEIPAETCSQOTOIUCQIUCNESEECSIYCYTTSTXCAUJIRENENPALSTETELIntroduction to Hematology—Level II

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