Hematocrits Hematology 101 Plasma White cells Red cells Blanche P Alter, MD, MPH, FAAP Clinical Genetics Branch Division of Cancer Epidemiology and Genetics Bethesda, MD Normal, Hemorrhage, IDA, Leukemia, Hemolysis, B12, P Vera Normal Peripheral Blood Aplastic Anemia Peripheral Blood Red blood cells Platelets White blood cells Red Cells Reticulocytes • Contain a red pigment, hemoglobin Red cells • Carry oxygen from the lung to other newly tissues that need it released • Muscles, liver, kidney, heart, brain from bone • Normally live 4 months marrow 1 Fetal Hemoglobin Platelets Kleihauer- • Help blood clot Betke stain • Live 7-10 days • Low numbers can lead to: • Bruising • Petechiae (tiny red dots) • Nosebleeds • Internal bleeding Platelets Types of White Cells (Leukocytes) White Blood Cell Functions Type Life Span • Neutrophils - eat bacteria and fungus Phagocytes (eaters): • Lymphocytes - direct the other cells and Neutrophil hours make antibodies Monocyte days • Monocytes - eat particles coated with Eosinophil hours antibody Basophil hours • Eosinophils - allergies and fight parasites Lymphocytes months-years • Basophils - allergies Neutrophils (Phagocytes) Lymphocytes • Polymorphonuclear (PMN), segmented, • Regulate other white cells granulocytes • Bands, juveniles = early forms • Make antibodies • First line of defense against bacterial • Proteins that act as flags to infection is intact skin and lining of the stic k to bac ter ia an d v iruses mouth, throat and intestines • Tell other cells to eat things • Second line of defense is neutrophils, which eat bacteria and kill them • Low neutrophil number increases susceptibility to bacterial and fungal infections 2 Monocytes CBC Machine • Phagocytes • Draw blood from the • Become tissue macrophages tube into an electronic • Cells in the tissues that eat counter particles tagged with antibodies • Result is called the complete blood count (CBC) Y Bacterium tagged by an antibody Blood Counts Red Cells • Hemoglobin (Hb, Hgb) WBC RBC • 12-15 grams/100 ml (g/dl) [lower Hb for children] Hct MCV • Hematocrit (Hct) MCH • 35 to 45% MCHC RDW Plat Anemia = Low Hb/Hct (H/H) MPV Platelets White Blood Cells (Leukocytes) • Platelet count (Plt) • WBC = white blood cell count • 150,000 to 400,000/μl • 5000–10,000/μl, 5 – 10 thousand/μl • WBC differential Thrombocytopenia = low platelets • % Neutrophils, bands, lymphocytes, monocytes, eosinophils, basophils Leukopenia = low WBC 3 Absolute Neutrophil Count (ANC(ANC) CBC Summary • ANC = WBC x % Neutrophils • Quick and easy assessment of numbers • e.g. WBC = 5000/μl, 30% neutrophils of blood cells • ANC = 5000 x 0.30 = 1500/μl • Relatively inexpensive • Normal: above 1500/μl • No single test tells us more about a blood • OK: above 500 disorder • Low: 200-500 • Measures all three cell types (RBC, WBC, • Very low: below 200 platelets) Neutropenia = low neutrophils • Provides other valuable details Causes of Anemia Definitions • Decreased production • Aplastic Anemia (AA): • Decreased reticulocytes • Pancytopenia due to decreased • Increased destruction production • Hypocellular bone marrow • Increased reticulocytes • Leukemia: • Blood loss • Malignant proliferation of immature cells • Increased reticulocytes • Myelodysplastic syndrome (MDS): • Cytopenia with hypercellular bone marrow Bone Marrow Equipment Bone Marrow Biopsy Normal Aplastic Aspirate Biopsy 4 Aplastic Anemia Bone Marrow Normal Bone Marrow Aspirate 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 CFUCFU--EE and BFUBFU--EE Dysplastic Marrow in MDS • Erythroid: megaloblastic, multinucleation, nuclear fragments, increased immature forms, ring sideroblasts • MlidMyeloid: iditfincreased immature forms, hypo/hyper-granulation • Megakaryocytes: hypo-/hyper-lobulated, small forms, increased nuclear- cytoplasmic ratio Bone Marrow in MDS - myeloid and Bone Marrow in MDS - Erythroid megakaryocytic 6 FAB CLASSIFICATION WHO Classification RCUD: refractory cytopenia with unilineage • No MDS dysplasia (>10% cells in one lineage) • RA = refractory anemia RA, RN, RT: anemia, neutropenia, thrombocytopenia • RARS = ring sideroblasts RARS: ring sideroblasts • RAEB = RA with excess blasts (5-20%) RCMD: multilineage dysplasia (>2 lineages) • CMML = chronic myelomonocytic RAEB-1: 5-9% blasts leukemia, PB monocytes >1000/μL RAEB-2: 10-19% blasts • RAEBT = RA in transformation MDS-U: unclassified: dysplasia <10% cells, + clone MDS del(5q): anemia with isolated del(5q) French-American-British 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.