Hematology 101. Plasma White cells. Red Cells. Red cells. newly released. marrow

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Hematocrits Hematology 101 Blanche P Alter, MD, MPH, FAAP Clinical Genetics Branch Division of Cancer Epidemiology and Genetics Bethesda, MD Plasma White cells Red cells Normal, Hemorrhage, IDA, Leukemia, Hemolysis, B12, P Vera Normal Peripheral Blood Aplastic Anemia Peripheral Blood Red blood cells White blood cells Red Cells Contain a red pigment, hemoglobin Carry oxygen from the lung to other tissues that need it Muscles, liver, kidney, heart, brain Normally live 4 months Reticulocytes Red cells newly released from bone marrow 1

Fetal Hemoglobin Kleihauer- Betke stain Help blood clot Live 7-10 days Low numbers can lead to: Bruising Petechiae (tiny red dots) Nosebleeds Internal bleeding Types of White Cells (Leukocytes) Type Life Span Phagocytes (eaters): Neutrophil hours Monocyte days Eosinophil hours Basophil hours Lymphocytes months-years White Blood Cell Functions Neutrophils - eat bacteria and fungus Lymphocytes - direct the other cells and make antibodies Monocytes - eat particles coated with antibody Eosinophils - allergies and fight parasites Basophils - allergies Neutrophils (Phagocytes) Polymorphonuclear (PMN), segmented, granulocytes Bands, juveniles = early forms First line of defense against bacterial infection is intact skin and lining of the mouth, throat and intestines Second line of defense is neutrophils, which eat bacteria and kill them Low neutrophil number increases susceptibility to bacterial and fungal infections Lymphocytes Regulate other white cells Make antibodies Proteins that act as flags to stick to bacteria and viruses Tell other cells to eat things 2

Monocytes Phagocytes Become tissue macrophages Cells in the tissues that eat particles tagged with antibodies CBC Machine Draw blood from the tube into an electronic counter Result is called the complete blood count (CBC) Y Bacterium tagged by an antibody Blood Counts WBC RBC Hb Hct MCV MCH MCHC RDW Plat MPV Red Cells Hemoglobin (Hb, Hgb) 12-15 grams/100 ml (g/dl) [lower for children] Hematocrit (Hct) 35 to 45% Anemia = Low Hb/Hct (H/H) Platelet count (Plt) 150,000 to 400,000/μl Thrombocytopenia = low platelets White Blood Cells (Leukocytes) WBC = white blood cell count 5000 10,000/μl, 5 10 thousand/μl WBC differential % Neutrophils, bands, lymphocytes, monocytes, eosinophils, basophils Leukopenia = low WBC 3

Absolute Neutrophil Count (ANC) ANC = WBC x % Neutrophils e.g. WBC = 5000/μl, 30% neutrophils ANC = 5000 x 0.30 = 1500/μl Normal: above 1500/μl OK: above 500 Low: 200-500 Very low: below 200 Neutropenia = low neutrophils CBC Summary Quick and easy assessment of numbers of blood cells Relatively inexpensive No single test tells us more about a blood disorder Measures all three cell types (RBC, WBC, platelets) Provides other valuable details Causes of Anemia Decreased production Decreased reticulocytes Increased destruction Increased reticulocytes Blood loss Increased reticulocytes Definitions Aplastic Anemia (AA): Pancytopenia due to decreased production Hypocellular bone marrow Leukemia: Malignant proliferation of immature cells Myelodysplastic syndrome (MDS): Cytopenia with hypercellular bone marrow Bone Marrow Equipment Bone Marrow Biopsy Normal Aplastic Aspirate Biopsy 4

Normal Bone Marrow Aspirate Aplastic Anemia Bone Marrow Aspirate Erythroid (red cells) Myeloid (white cells) Bone Marrow Iron Leukemia Bone Marrow Hematopoiesis Formation and development of blood cells Takes place in the bone marrow Involves stem cells 5

Hematopoiesis BM Cultures CFU-E: colony-forming unit, erythroid BFU-E: burst-forming unit, erythroid CFU-C: colony-forming unit in culture CFU-GM: colony-forming unit, granulocyte-macrophage CFU-E and BFU-E Dysplastic Marrow in MDS Erythroid: megaloblastic, multinucleation, nuclear fragments, increased immature forms, ring sideroblasts Myeloid: increased immature forms, hypo/hyper-granulation Megakaryocytes: hypo-/hyper-lobulated, small forms, increased nuclearcytoplasmic ratio Bone Marrow in MDS - Erythroid Bone Marrow in MDS - myeloid and megakaryocytic 6

FAB CLASSIFICATION No MDS RA = refractory anemia RARS = ring sideroblasts RAEB = RA with excess blasts (5-20%) CMML = chronic myelomonocytic leukemia, PB monocytes >1000/μL RAEBT = RA in transformation French-American-British WHO Classification RCUD: refractory cytopenia with unilineage dysplasia (>10% cells in one lineage) RA, RN, RT: anemia, neutropenia, thrombocytopenia RARS: ring sideroblasts RCMD: multilineage dysplasia (>2 lineages) RAEB-1: 5-9% blasts RAEB-2: 10-19% blasts MDS-U: unclassified: dysplasia <10% cells, + clone MDS del(5q): anemia with isolated del(5q) Hematopoiesis Blood and Marrow MDS Study Aspirate: Morphology Biopsy: Cellularity Cytochemistry: PAS, MPO, dual esterase, iron Flow cytometry: Lymphocytes, granulocytes Oncogenes: p53, p21 Cytogenetics: Classical G banding, FISH (fluorescence in situ hybridization), CGH (comparative genomic hybridization) Prepared by www.marrowfailure.cancer.gov Blanche P Alter, MD, MPH National Cancer Institute Greg Kato, MD National Heart, Lung, and Blood Institute M Tarek Elghetany, MD University of Texas Medical Branch 7