Tim R. Randolph. PhD, MT(ASCP) Chair and Associate Professor Department of Biomedical Laboratory Science Saint Louis University
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1 Tim R. Randolph. PhD, MT(ASCP) Chair and Associate Professor Department of Biomedical Laboratory Science Saint Louis University
2 Anemias Over 30 types Myeloproliferative Neoplasm Polycythemia Leukemia AML:M6
3 Two approaches RBC size MCV Microcytic Normocytic Macrocytic Balance between i production & h destruction Requires many lab tests All data must be in to make diagnosis
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5 Iron Metabolism Problems Iron testing DISEASE SERUM FERRITIN (NG/ML) SERUM IRON (UG/DL) IRON-BIND CAPACITY (UG/DL) TRANS. SATUR. (%) TISSUE IRON STORES Normal Iron Deficiency Anemia Male female Sideroblastic Anemia Anemia of Inflammation -N
6 Thalassemias QUANTITATIVE reduction in Hb synthesis 6 normal human globin genes Alpha, beta, gamma, delta (epsilon, zeta) About 435 mutations 2 major types of thalassemia Alpha thalassemia Beta thalassemia Suspect when Inherited Mediterranean nationality Normal iron studies
7 Thalassemia
8 Thalassemia Alpha-Thalassemia Reduction in alpha containing Hb HbA, HbA 2, HbF Increase in non-alpha containing Hb Hb Barts ( g 4 ), HbH ( b 4 ) Beta Thalassemia Reduction in beta containing Hb HbA Increase in non-beta containing Hb HbA 2, HbF
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10 Hemoglobinopathies QUALITATIVE change in Hb amino acid sequence Over 1,000 mutations Most cause little to no symptoms Most common types Sickle cell (HbS) (valine for glutamic acid at 6 th position) HbC (Lysine for glutamic acid at 6 th position) HbE (Lysine for glutamic acid at 26 th position) HbO (Lysine for glutamic acid at 121 st position) HbD (Glutamine for glutamic acid at 121 st position)
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13 Membrane Disorders Hereditary Spherocytosis Spherocytes Hereditary Elliptocytosis Elliptocytes Hereditary Pyropoikilocytosis Spherocytes & Schistocytes Hereditary Stomatocytosis Stomatocytes Hereditary Xerocytosis Blister cells/helmet cells
14 Enzyme Deficiencies G6PD Deficiency X-linked (males) Crisis occurs following exposure to oxidative drugs Primaquine, sulfonamides, antibiotics, analgesics, fava beans, Vitamin K & C, etc. Sudden hemolytic crisis (Hemoglobinuria) Heinz Bodies Pyruvate Kinase Autosomal Milder symptoms No Heinz Bodies
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16 Decreased production Aplastic Anemia Pancytopenia Normal morphology Pure Red Cell Aplasias Decrease in RBCs only Congenital Dyserythropoetic Anemias Dysplastic morphology (macro, multi-lobed, cell bridges) 4 types (CDA 1,2,3,4)
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22 Myeloproliferative Neoplasms Lab Tests PV CML ET PM RBC, Hb, Hct hhh N-i N-i i WBC N-h hhh N-h h to hh Platelets h hori hhh horior N BM Fibrosis Absent - h Absent - h Absent - h hhh Immature Neut None hhh Rare hh Spleen Size h h N-h h LAP N-h i N-h horior N Ph1 Absent Present Absent Absent JAK2 97% 0% 50-60% 50-60%
23 Myelodysplastic Disorders Disorder Peripheral Blood Bone marrow RA RARS RAEB CMML Refractory macrocytic anemia <1% blasts Refractory anemia with dimorphic RBCs Occasional neutropenia & thrombocytopenia <1% blasts Anemia, leukopenia, thrombocytopenia (>2) Dysgranulopoiesis, Dysthrombopoiesis <5% blasts >1x10 9 /L monocytes with abnormal forms Mild anemia and thrombocytopenia Neutrophil precursors Dysthrombopoiesis <5% blasts Increased serum and urine muramidase <5% type I & II blasts Dyserythropoiesis Megaloblastic <5% type I & II blasts >15% ringed sideroblasts Dyserythropoiesis Megaloblastic Dysgranulo & megakaryopoiesis 5-20% type I & II blasts Dyserythro, granulo, megakaryopoiesis Abnormal promyelocytes 5-20% blasts, abnormal & immature monocytoid cells Increased myelocytes
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25 AML BM % M0 M1 M2 M3 M4 M5 M6 M7 Erythroblasts < 50% ANC < 50% ANC < 50% ANC < 50% ANC < 50% ANC < 50% ANC > 50% ANC < 50% ANC Myeloblasts >20% MPO-EM >90% >3 MPO >20% 20-89% >20% NEC >20% NEC >20% NEC >20% NEC >20% NEC Myeloid <10% + Monos <10% + Monos >10% Mostly Pros 20-80% <20% N/A N/A Monocytic <10% + Neutrophil <10% + Neutrophil <20% <20% 20-80% >5x10 9 >80a <80b Eosinophils N/A N/A N/A N/A >5%=M4E N/A N/A N/A MPO anti-mpo + (>3%) e, + m - SBB - + (>3%) e, + m - SE e, + m - NSE - +/- +/- +/ PAS - Diffuse Diffuse Diffuse Diffuse Diffuse N/A N/A
26 CD Marker Progenitor (Pro-B) CALLA (Early Pre-B) Pre-B B-Cell Pro-T Pre-T Cortical T Medullary T TdT-Lym /- +/- +/- +/- HLA-DR-Ly /- +/- +/- +/- CD34 (stem) + +/ /- +/- - - CD19 (B) CD /- - +/- +/- +/- +/- CD22 + (cyto) + (cyto) + (surf) + (surf) CD20 - +/ cm sig - - +/ CD1a CD CD CD CD T H OR CD T S/C
27 Miscellaneous Chronic Malignancies Disease WBC Diff Abn Cell BM Prognosis Other CLL Multiple Myeloma Waldenstrom s Macroglobulin Hodgkin s Lymphoma hhh h Lymph Norm Norm Norm Norm Plasma Cell Normal Plasma- Cytoid Ly Lg Aty Lym Reactive Lymph Plasma Cell Plasmacytoid Lymph Lymphoid LN NHL Norm Normal Lymphoid LN Mycosis Fungoides Hairy Cell Leukemia Norm To h Pancy Normal Sezary Cell h Lymph h HC Sezary Clefted T helper Hairy Cells h Lymph Plasma Cell Plasmacytoid Lymph Reed- Sternberg Lymphoid Normal Skin Fibrotic h HC A/B Good C Chemo Poor Chemo Poor Chemo Good Chemo/Rad Poor Chemo/Rad Skin-2-10y Sezary 1yr Moderate 5-10 yrs Older 2:1 male h IgG h IgA h IgM 20-30yo 50-60yo Mid-age Older Skin Plaques 7:1 M:F TRAP
28 Questions?????
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