Indiana University Bloomington



Hematopoietic Assignments and ObjectivesReadingsBasic Robbins Chapter 11 or Big Robbins Chapters 13 and 14SlidesHematologic Disorders These are thirteen cases with brief clinical scenarios with peripheral blood smears; no blood smears are in the slide box. A CBC review and a normal blood smear are also present for review. These are the same slides in Module 27 listed below.Lymphatic System Slides 60, 62, 67, 84, 111, 160, 167, 206, and normal lymph nodeThese are glass slides also available via virtual microscopy.Online clinical casesCase 11 Mr. Herbert: A man complaining of lethargyCase 17 Mrs. Talbot: Woman with a neck massModule 24 Coagulation tutorialModule 19 Leukemia reviewModule 27 These are the same peripheral blood smears in the Hematologic Disorders listed above in the Slides section.ObjectivesHematopoiesisEmbryonic hematopoiesisNormal anatomy of bone marrow with trilinear hematopoiesisNormal anatomy of blood with automated and derived indicesRed cell disordersClassifications of anemia by MCV and by etiologyAnemia of blood lossHemolytic anemiasHemoglobin catabolismIntrinsic (intracorpuscular) hemolysisHereditary spherocytosisSickle cell anemiaThalassemiasG6PD deficiencyParoxysmal nocturnal hemoglobinuriaExtrinsic (extracorpuscular) hemolysisImmune-mediated hemolytic anemiasWarm antibody immunohemolytic anemiaCold antibody immunohemolytic anemiaNon-immune hemolytic anemiasMechanical destructionMicroangiopathic hemolytic anemiaMalariaAnemias of diminished erythropoiesisIron deficiency anemiaAnemia of chronic diseaseMegaloblastic anemiasAplastic anemiaPure red cell aplasiaMyelophthisic anemiaPolycythemiaAbsolute and relative erythrocytosisWhite cell disordersLeukopeniaReactive leukocytosisLeukemoid reactionInfectious mononucleosisReactive lymphadenitisAcute and chronic nonspecific lymphadenitisCat scratch diseaseNeoplastic proliferations of white cellsClassification of neoplasms based on cell of origin and differentiationLymphoid neoplasmsClonality of lymphocytesMonoclonal protein, genetic rearrangement, translocationPrecursor (immature) B and T acute lymphoblastic leukemia/lymphomaPeripheral (mature) B cell neoplasmsChronic lymphocytic leukemia/small lymphocytic lymphomaFollicular lymphomaMantle cell lymphomaDiffuse large B cell lymphomaBurkitt lymphomaPlasma cell tumorsMGUSSolitary plasmacytomaMultiple myelomaLymphoplasmacytic lymphoma/ Waldenstr?m macroglobulinemiaHodgkin lymphomaExtranodal marginal zone lymphomaHairy cell leukemiaPeripheral (mature) T cell neoplasmsCutaneous T cell lymphoma (mycosis fungoides)Adult T cell leukemia/lymphomaMyeloid neoplasmsMyelodysplastic syndromesAcute myelogenous leukemiasFAB M3/APLFAB M4/Myelomonocytic LeukemiaChronic Myeloproliferative neoplasmsChronic myelogenous leukemiasPolycythemia veraPrimary myelofibrosisEssential thrombocythemiaHistiocytic neoplasmsLangerhans cell histiocytosesBleeding disordersPrimary hemostasisAdhesion, Activation, AggregationSecondary hemostasisIntrinsic and extrinsic pathwaysAntithrombotic mechanismsInhibitory effect on primary hemostasisInhibitory effects on secondary hemostasisFibrinolysisLaboratory testingPlatelet assessmentCoagulation assessmentPlatelet disordersNeonatal and post-transfusion immune reactionImmune Thrombocytopenic purpura (ITP)Heparin Inducted Thrombocytopenia (HIT)HIV-associated thrombocytopeniaThrombotic Thrombocytopenia Purpura/Hemolytic Uremic Syndrome(TTP/HUS)Bernard Soulier diseaseGlanzmann thrombastheniaVon Willebrand diseaseCoagulation disordersFactor VIII deficiency (Hemophilia A)Factor IX deficiency (Hemophilia B)Disseminated Intravascular Coagulopathy (DIC)Spleen and thymusSplenomegaly/hypersplenismDiGeorge syndromeMediastinal tumors5116830-75120500Hematopoietic and Lymphoid SystemsBasic Robbins Chapter 11Mark E. Bauman, M.D.Hematopoiesis(Most material below not in text)3rd week gestational age5602605114935003rd month gestational age4th month gestational age18 years Hb AHb A2Hb F570420510096500red/white marrowextramedullary hematopoiesisstem cells57848504064000Normal anatomy of bone marrowCell/fat ratio56457859144000Hypoplasia/hyperplasiaMyeloid/erythroid ratioAvg life span RBCPolyPlatelet5139690539750059474105397500Erythroid maturation5116830381000Granulocytic maturation Megakaryocytes5823585-19240500Normal anatomy of peripheral bloodErythrocytesHb content: Normochromic/ hypochromic/ hyperchromic57746908318500Polychromatophilia/polychromasia (standard Wright stain) Reticulocytes (retic stain showing RNA still synthesizing Hb)Reticulocyte countPercentage: 0.5 – 1.5% (Except in newborns 2.5 – 6.5)Absolute: 24 – 84 x 109Reticulocytes production index/Corrected reticulocyte count compensates fordecreased # RBCincreased life span of reticulocyte (early marrow exit)Consumption vs Production etiology of anemiaSize: Normocytic/microcytic/macrocytic; variation =Shape: Elliptocytes, spheroctyes, target cells, schistocytes, acanthocytes561784546355Multiple images020000Multiple images544893566040Multiple images020000Multiple imagesErythrocyte cytoplasmic inclusions:Basophilic stipplingPappenheimer bodiesHowell-Jolly bodiesRouleaux formationRBC IndicesRBC countMCVHctMCHHbMCHCRDWLeukocytesTotal WBC/mm3% polysAbsolute polys% lymphsAbsolute lymphs% monos% eos% basosTotal WBC/mm3% lymphsRelative lymphocytosis?Absolute lymphocyte countAbsolute lymphocytosis?10,000706,0007030,0003010,00030PlateletsTotalQuality vs QuantityRed Cell DisordersAnemia =reduction of O2 transport capacity in bloodAnemias classified by MCV105473512763500Anemias classified by Underlying Etiology***Table 11-1***1. A.B.2. A.B.3.Anemias of Blood Loss: HemorrhageAcute vs chronic blood lossHct/HbReticulocytesHemolytic AnemiasIncreased RBC destruction: Intrinsic and extrinsic abnormalitiesEPOLDHReticulocytesBone marrow4568825-4000500Hemoglobin catabolism1604645113030Hemoglobin → Heme → Biliverdin → Bilirubin00Hemoglobin → Heme → Biliverdin → Bilirubin28003502032000unconjugated hyperbilirubinemiahemoglobinemiahemoglobinuriahaptoglobinGilbert syndromeDubin-Johnson syndromeTable 15-3: Main causes of jaundiceInstrinsic (intracorpuscular) hemolysis48571151524000Hereditary spherocytosis (Figures 11-1 and 11-2)48571156921500Spherical erythrocytes secondary to an inherited defect of red cell membrane skeleton proteins 54209955651500513016510350500Osmotic fragility57658001587500Clinical:Sickle Cell AnemiaHemoglobinopathy599694010096500Hb S substitution of valine for glutamic acid at amino acid 6 of the globin chainHb SSHb ASHbC substitution of lysine for glutamic acid at amino acid 6 of β globin chainChronic hemolytic anemiaClinical onset in homozygotesCongestion, thrombosis, infarctionVeno-occlusive crisesAutosplenectomy4471035128905005647690190500DX: Hb electrophoresis/HPLCThalassemia Syndromes Thalassa + emia =(Figures 11-5 and 11-6, Table 11-3)Pathogenesis: relative excess of insoluble, unstable chains secondary to ineffective erythropoiesisPeripheral blood/anemia/splenic sequestration Thalassemia525462512573000Each chromosome 16 has two genes for alpha; typically loss of entire geneI-/silent carrierII- -/-thal trait, Asian-/--thal trait, AfricanIII- -/-Hb H disease, -globin tetramers = Hb HIV- -/- -Hb Barts, hydrops fetalis, -globin tetramers = Hb Barts ThalassemiaEach chromosome 11 has a single gene for beta.Typically point mutations (promoters, terminators, splicing).= normal gene49841151714500+ thal= decreased production (variable amount produced)0 thal = total absence of beta globin chain/=/+ or /0=/0 or +/+= +/+ or 0/0=51644551397000Hb electrophoresis/HPLC minor↑Hb A2 (4-8%) majorHb A2 ↑ or ↓; Hb F usually ↑Clinical courseSkeletal deformities51111157366000HemochromastosisGlucose-6-phosphate dehydrogenase deficiencyOne example of an erythrocyte enzyme defectDefective hexose monophosphate shunt incapable of regenerating reducedGlutathione (GSH). GSH needed for inactivation of intracellular oxidants, e.g. sulfonamide, primaquine, infectious agents, fava beans, H2O2 from phagocytes during infections482155513716000Heinz bodies (Figure 11-7)54336958636000Bite cells: (Fig 13-8) Genetics: Clinical: enzyme synthesis vs enzyme stabilityParoxysmal Nocturnal HemoglobinuriaSomatic mutation of pluripotential stem cell decreased glycosyl phosphatidyl inositol (GPI: a phospolipid anchoring non-transmembrane proteins); decreased GPI decreased GPI-linked proteins regulating complement increased sensitivity of RBCs to complement MisnomerHam’s test43465757302500Flow cytometry for CD 55 and CD 59 (GPI-linked proteins)FLAER: fluorescent labeled proaerolysin (binds to PGI)Rx: Eculizumab54336956477000Extrinsic (extracorpuscular) hemolysisImmune-mediated hemolytic anemiaAnti-RBC antibodies and complement-mediated RBC hemolysisDirect Antibody Test (D.A.T.) = Coomb’s test547624019812000Indirect Antibody Test (I.A.T.) = Indirect Coomb’s testWarm Antibody Immunohemolytic AnemiaTemperatureIgG or C3Idiopathic 75%Immune disordersSpherocytesCold Antibody Immunohemolytic AnemiaTemperatureIgMOpsonizationAgglutinationNon-immune hemolytic anemiasMechanical etiologiesMicroangiopathic hemolytic anemiaDIC, TTPSchistocytes58997858953500Malaria1 million deaths annually; endemic in Asia and AfricaPlasmodium species: P. falciparum, P. malariae, P. vivax, P. ovale596963515938500MosquitoParasite life cycle56870604699000Clinical596963513208000Anemias of Diminished Erythropoiesis55505352603500Iron deficiency anemia (Figure 11-9)Iron functionsIron absorption and balanceFerroportin 1/hepcidin24542755016500Serum ironTIBCTransferrin% transferrin saturationFerritin57931052413000Hemosiderin/hemosiderosis5444490825500Hemochromatosis (page 629, figure 15-25)Iron deficiency55314853746500Iron deficiency anemia (Figure 11-10)MCVMCHRDWPlateletsFerritinFree erythrocyte protoporphyrinAnemia of chronic diseaseDefective utilization of iron (present in adequate amounts) secondary to a defectin iron transfer from the storage pool to erythroid precursorsFerroportin 1/hepcidinClinical settingsMCVRDWPlateletsFerritinMegaloblastic Anemias Impaired DNA synthesisMegaloblasts: impairment of cell maturation and division; normal RNA and587438516510000protein synthesis; nuclear/ cytoplasmic dysynchrony; ineffective hematopoiesisBone marrow erythroid and granulocyte precursors56654703111500MacrocytosisMCVReticPlateletsNeutrophils B12 (Cobalamin)FolateSources/storage:Deficiency: Pernicious anemia: One form of megaloblastic anemia secondary to defects of intrinsic factor406146016383000Physiologic absorption of B12Haptocorrin/R-binderIntrinsic factorCubilin/megalinTranscobalaminSerum antibodies1.2.3.Additional etiologies of malabsorptionCNS Changes: spinal cord demyelinization of dorsal and lateral tracts (sensory ataxia, paresthesias of extremities)Aplastic anemiaTrilinear aplasiaEtiologiesPure red cell aplasiaAssociationVirus60871101270000Myelophthisic anemia57410356921500LeukoerythroblastosisPolycythemiaPolycythemia/erythrocytosisRelative erythrocytosis Absolute erythrocytosisPrimary: RBC production not regulated by EPOSecondary: RBC production regulated by EPOAppropriateInappropriateSurreptitiousWhite Cell DisordersNon-neoplastic Disorders of White CellsLeukopeniaNeutropenia/agranulocytosisDecreased productionIncreased consumptionReactive leukocytosisReview Table 11-6 Causes of Leukocytosis (page 426 in Basic Robbins)Leukemoid reaction463613513208000Infectious mononucleosisClinical EBV Monospot test (rapid heterophile antibody); serologyAtypical lymphocytosis Lymphadenopathy, hepatosplenomegalyAssociations 6156960285750056654702857500516064528575001.2.3.521970016256000Reactive lymphadenitis59455052476500Normal lymph node structureAcute nonspecific lymphadenitis6009005806450054483004000500594106013652500Chronic nonspecific lymphadenitisFollicular hyperplasia59213756921500Paracortical hyperplasiaSinus histiocytosis595503063500050190406413500Cat scratch diseaseBartonella henselaeCervical, axillary adenopathy: stellate necrotizing granulomataNeoplastic Proliferations of White Cells(Note: The following material is somewhat different from the order of presentation in the text.)39274752413000LymphomaLeukemiaMyelodysplasiaMyeloproliferative neoplasms1.2.3.4.Lymphoid neoplasms5125720222250057994551841500Benign vs malignantClonality55365654318000460438515113000568515546990001. Monoclonal protein (surface antigen receptor or secreted globulin)5768975114935002. Genetic rearrangement: PCR/Electrophoresis of amplified DNA546227012128500569214011176000564769011239500608012553975003. Chromosomal translocation: FISH (Fluorescent in situ hybridization)53752758953500 Classification schemes for lymphomas attempt to define distinct clinic-pathologic entities, based on cell morphology, origin, maturity, immunophenotype, genotype, and clinical features. ***Table 11-7 WHO Classification of Lymphoid Neoplasms ***Most lymphomas resemble some stage of B or T cell differentiation. (Figure 11-13)5754370254000B cell:T cell:NK cell:Nodal:Extranodal:Non-Hodgkin lymphoma:Hodgkin lymphoma:B cellT cellPrecursor (immature)Peripheral (mature)Most common lymphomas are derived from germinal center or post germinal center B cells.57543701397000Immune abnormalities in lymphomasNHL lymphomas are systemicPrecursor (immature) B and T cell leukemia/lymphoma = Acute lymphoblastic leukemia/lymphoblastic lymphomaALL5824855711200058648603238500Morphology57886607302500MolecularClinicalAleukemic leukemiaDistinguished from AMLPeripheral (mature) B cell neoplasmsCLL/SLL: Chronic lymphocytic leukemia/small lymphocytic lymphomaMorphology58953407810500Lymph node589534013462000Blood590931063500Bone marrowImmunophenotypeClinicalSubsets of CLLCD38/Zap-70Richter transformation“Monoclonal B lymphocytosis”597662017145000545655517335500Follicular lymphomaMorphologyImmunophenotype59302651968500Molecular5976620131445005976620698500Clinical447865514795500Mantle cell lymphomaMorphologyImmunophenotypeMolecularClinicalLymphomatoid polyposisBlast variantDiffuse large B cell lymphoma5812790-63500Morphology (Figure 11-17)ImmunophenotypeMolecularClinicalEBV-associated DLBCLBurkitt lymphoma58997855842000493966558420003 types1)2)3)MorphologyMolecularc-MYC located on 8t(8;14) t(2;8)t(8;22)Multiple myeloma and related plasma cell tumors(Note: The following material is somewhat different from the order of presentation in the text.)45643805778500MorphologyMott cellSolitary plasmacytomaMultiple myelomaSecretory functionBence Jones proteinMGUSClinicalImmunosuppresionPeripheral bloodPathologic fractures/lytic lesionsHypercalcemiaMyeloma nephrosisLight chain (AL) amyloidosisPrognosis4578985-11112500Lymphoplasmacytic lymphomaWaldenstr?m macroglobulinemia/hyperviscosity syndromeHeavy chain disease45129452540000Hodgkin lymphoma: a B cell lymphomaHL NHLSiteSpreadNodal basedMorphology: Reactive cells plus Reed Sternberg cells5 subtypes: 4 Classical (nodular sclerosis, lymphocyte rich, mixed cellularity, lymphocyte depleted) and Nodular Lymphocyte PredominanceClassicalRS cells CD15 and CD30 positive; CD45 and CD20 negative 589534015494000530860015494000Nodular sclerosis with “Lacunar cells”Lymphocyte Predominance HLLymphohistiocytic variant RS cells (popcorn cells)CD15 and CD30 negative; CD45 and CD20 positiveEBVClinicalStaging and “B” symptomsPrognosis465772513017500Extranodal marginal zone lymphomaMorphologyMALTomaSitesAssociations502348514287500Hairy cell leukemiaMorphologyImmunophenotypeTRAP (outdated)ClinicalSpenomegalyBone marrow involvementPrognosisPeripheral (mature) T cell neoplasmsMycosis fungoides549275010477500Cutaneous T-cell lymphoma: patches, plaques, tumorsPautrier microabscessesSezary syndromeAdult T cell leukemia/lymphomaHTLV-1 and HTLV-2RNA retrovirusJapan, Caribbean, West AfricaMyeloid neoplasms(Note: The material on Myelodysplasia in this handout precedes that of acute myeloid leukemia. The Robbins text presents AML before Myelodysplasia.)Myelodysplastic syndromesWHO definition: A group of clonal myeloid neoplasms characterized by ineffective hematopoiesis that present clinically as cytopenia(s), dysplasia in one or more hematopoietic cell lines in the bone marrow, and risk of transformation to acute myeloid leukemia.Morphology52362101168400054705256096000Molecular: monosomy 5, monosomy 7; 5q-, 7q-, 20q-Subtypes: Refractory cytopenia with unileage dysplasia (RCUD), Refractory anemia with ring sideroblasts (RARS), Refractory cytopenia with multilineage dysplasia (RCMD), Refractory anemia with excess blasts-1 (RAEB-1), Refractory anemia with excess blasts-2 (RAEB-2), Myelodysplastic syndrome unclassified (MDS-U), MDS associated with isolated del (5q), Therapy-related MDS (t-MDS).ClinicalAcute myeloid leukemia = Acute myelogenous leukemia = AMLAt least 20% marrow blasts.5164455-4064000Morphology(Figures 11-14, 11-25)Auer rodsImmunophenotypeClinicalWHO Classification based on cell lineage, cell maturation, molecular changesAML with recurrent chromosomal translocationsAML with a translocation between chromosomes 8 and 21AML with a translocation or inversion in chromosome 16AML with changes in chromosome 11APL (M3), which usually has translocation between chromosomes 15 and 17AML with multilineage dysplasia?(more than one abnormal myeloid cell type is involved)AML related to previous chemotherapy or radiationAML not otherwise specified?(includes cases of AML that don't fall into one of the above groups; similar to the FAB classification)Undifferentiated AML (M0)AML with minimal maturation (M1)AML with maturation (M2)Acute myelomonocytic leukemia (M4)Acute monocytic leukemia (M5)Acute erythroid leukemia (M6)Acute megakaryoblastic leukemia (M7)Acute basophilic leukemiaAcute panmyelosis with fibrosisMyeloid sarcoma (also known as granulocytic sarcoma or chloroma)Undifferentiated or biphenotypic acute leukemias?(leukemias that have both lymphocytic and myeloid features). Sometimes called ALL with myeloid markers, AML with lymphoid markers, or mixed lineage leukemias.FAB M3t(15;17) retinoic acid receptor α (RARA) gene on 17PML gene on 1548431453746500ClinicalRx:500951513017500FAB M4FAB M6Chronic Myeloproliferative NeoplasmsClonal neoplasm of myeloid cells retaining capacity for terminal differentiationConstitutive tyrosine kinase activityPeripheral blood Bone marrowHepatosplenomegaly“Spent phase” or “blast crisis” 530225053340001. Chronic myelogenous leukemia (CML)Peripheral blood (Figure 11-26)DDx:Philadelphia chromosomeRxPrognosisAccelerated phaseBlasts crisis2. Polycythemia vera52635151333500Peripheral bloodEPOJAK2Thromboses/infarctions/ erythromelalgiaPrognosis/Rx3. Primary myelofibrosis519176017589500Peripheral bloodBone marrowExtramedullary hematopoiesisJAK2Prognosis4. Essential thrombocythemia546608067310005906135889000Peripheral bloodBone marrowJAK2Histiocytic neoplasmsTwo types of histiocytes: macrophages/histiocytes and dendritic cells Dendritic cells present antigens to initiate an immune response5530850889000Two types of dendritic cells: 1. Follicular dendritic cells within germinal centers2. Langerhans cells – a dendritic cell within the dermisCD1a positiveBirbeck granules: pentalaminar tubular structures on EM (tennis rackets)Langerhans cell histiocytoses (LCH)Unisystem LCHUnifocal unisystem LCH (“eosinophilic granuloma”)Erosive aggregates of LC’s, often in bone, skin or lungsMutlifocal unisystem LCH Multiple bony masses, often extending into soft tissuesHand-Schüller-Christian triad: calvarial bone defects, diabetes insipidus (posterior pituitary stalk involvement),exophthalmosMultisystem LCH (Letterer-Siwe disease)Seborrheic skin eruptions, hepatosplenomegaly, pulmonary lesions,destructive bone lesionsBleeding Disorders513715021145500(Note: The material presented below draws from chapters 3 and 11 of Basic Robbins. The order of this material does not follow the text. Some of the material is not in the text.)HemostasisPetechiae Purpura Echymosis Contusion Hematoma41402003238500Primary Hemostasis (Fig 3-7)1. Adhesion 2. Activation α (alpha) granulesδ (delta) granules/dense bodiesTxA2Arachidonic acid ------------------ Prostaglandin H2 -------------- TxA21.2.3.4.4237990-5969000Shape change1.2.3. AggregationSecondary Hemostasis: Coagulation SystemTransformation of plasma proenzymes activated enzymes with cofactors 496633528194000conversion of prothrombin → thrombin → conversion of fibrinogen fibrin with crosslinking by XIIIIntrinsic and extrinsic pathways (Figures 3-8, 3-9, 3-5)513524513906500418274511874500ThromboplastinVIIXII39268408509000IIIXIIICa++Antithrombotic mechanismsInhibitory effects on platelets (primary hemostasis) Intact endotheliumEndothelial productsDrugs (Chart near end of this handout)Inhibitory effects on coagulation (secondary hemostasis) (Figure 3-6)Anti-thrombin III517969512509500AT III is activated byActivated AT III functions to ThrombomodulinThrombomodulin functions to1.2. activate Protein CActivated Protein C inactivatesActivated Protein C Resistance/Factor V LeidenDNA PCR for codon 506 a.a. substitutionProtein S is a cofactor for Protein CTissue Factor Pathway Inhibitor (TFPI)Drugs (Chart near end of this handout)Unfractionated heparin and low molecular weight heparin-643255787400033693107874000Fibrinolysis (Figure 3-11)Plasminogen activated toactivated by1.2.3.Plasmin produces48742601397000Fibrinolysis is controlled by1.2.With bleeding disorders, history comes first: onset, type of bleeding, family historyPlatelet disorderCoag disorderPetechiaeDeep hematomasHemarthrosesDelayed bleedingMucosal bleedingLab tests for platelet functionBleeding time57683405651500576834015113000Platelet function analyzer (PFA) aggregation studies(Selected) Lab tests for coagulation functionActivated partial thromboplastin time (PTT)Prothrombin time (PT)INRINR = (PT patient/PT normal)ISIThrombin time1.2.51816007747000ReptilaseRussell viper venomMixing Studies5 y.o. male with a maternal uncle who died of bleeding following cholecystectomy. No previous episodes of bleeding in the 5 y.o. Now presents for herniorrhaphy. Screening pre-op.PTPTTPltDx:New born female returns to hospital with persistent bleeding from the umbilicus. No family history of bleeding.PTPTTPltDx:62 y.o. female with right upper quadrant pain consistent with cholecystitis. History of coronary artery disease and diabetes. No history of bleeding.PTPTTPltDx:4 y.o. girl with Hb 4.6 g/dL and recurrent epistaxis. Maternal grandmother had “easy bruising.”PTPTTPltDx:30 y.o. male with acute onset of fever and severe lethargy. Markedly increased white cell count with blasts.PTPTTPltDx:Platelet DisordersPlatelet Quantity: production vs consumptionProduction problemBone marrowConsumption problemSequestration/hypersplenismNeonatal and post-transfusion immune reactionITP (Immune Thrombocytopenic purpura)Immunologically mediated destruction of platelets479361512700000AcuteChronicAutoantibodiesPT/PTT/BMBxRxHIT (Heparin-induced Thrombocytopenia)51479458636000HIV-associated Thrombocytopenia:CD 4 receptors on megakaryocytesTTP/HUS (Thrombotic Thrombocytopenia Purpura/Hemolytic Uremic Syndrome) Thrombotic MicroangiopathiesTTP PentadFormation of55556154064000VWF metalloprotease defectADAMTS 13 (A Disintegrin-like And MetalloproteaseWith ThromboSpondin, the 13th member)Therapy:HUS etiologyPT/PTTPlatelet Quality Bernard Soulier DiseaseGlanzmann’s thrombastheniaStorage pool disorder46291501524000Von Willebrand Disease (Figure 11-29)VWF functions:1.2. t ? for VIII with vWF = without vWF =InheritanceClinical findingsPlatelet count PT PTTPlatelet function assayFVIII activityvWF AgvWF activity/Ristocetin testMultimer studies/Subtypes of vWDRxCoagulation DisordersFactor VIII Deficiency (Hemophilia A)InheritanceClinical findingsRange of VIII activityPlatelet countPTPTTPlatelet function assayFVIII activityRxFactor IX Deficiency (Hemophilia B, Christmas Disease)Clinical findingsLab testingFactor X1 Deficiency (Hemophilia C)Disseminated Intravascular Coagulation (DIC) (Figure 11-28)Activation of coagulation with microthrombi formation with microangiopathic hemolytic anemia, coupled with active fibrinolysis PT PTTPlatelet countFibrinogenD-dimerEtiologies 509524011430000852170-2286000-6057903365500Spleen and ThymusSpleenSplenomegaly ≠ hypersplenismCommon causes of massive, moderate and mild splenomegaly: page 456 Basic RobbinsThymus545655517335500Bone marrow progenitor cells migrate to the thymus and give rise to mature T-cellsThymic hypoplasia: DiGeorge syndromeThymic hyperplasia associated withThymomasMediastinal tumorsTTTT(End of Hematopoietic handout) ................
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