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Hematology 101 Plasma White cells Red cells Blanche P Alter, MD, MPH, FAAP Clinical Genetics Branch Division of Epidemiology and Genetics Bethesda, MD

Normal, Hemorrhage, IDA, , , B12, P Vera

Normal Peripheral Aplastic Peripheral Blood

Red blood cells

Platelets

White blood cells

Red Cells

• Contain a red pigment, Red cells • Carry from the to other newly tissues that need it released • Muscles, , , , brain from • Normally live 4 months marrow

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Kleihauer- • Help blood clot Betke stain • Live 7-10 days • Low numbers can to: • Bruising • Petechiae (tiny red dots) • • Internal

Platelets

Types of White Cells (Leukocytes) White Blood Functions

Type Life Span • - eat and (eaters): • - direct the other cells and hours make days • - eat particles coated with hours hours • - and fight parasites Lymphocytes months-years • - allergies

Neutrophils (Phagocytes) Lymphocytes

• Polymorphonuclear (PMN), segmented, • Regulate other white cells • Bands, juveniles = early forms • Make antibodies • First line of defense against bacterial • that act as flags to is intact and lining of the stic k t o b act eri a and 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

2 Monocytes CBC Machine

• Phagocytes • Draw blood from the • Become tube into an electronic • Cells in the tissues that eat counter particles tagged with antibodies • Result is called the

(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 • (Hct) MCH • 35 to 45% MCHC RDW Plat Anemia = Low Hb/Hct (H/H) MPV

Platelets White Blood Cells (Leukocytes)

count (Plt) • WBC = white count • 150,000 to 400,000/μl • 5000–10,000/μl, 5 – 10 thousand/μl • WBC differential = 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) = low neutrophils • Provides other valuable details

Causes of Anemia Definitions

• Decreased production • (AA): • Decreased reticulocytes • due to decreased • Increased destruction production • Hypocellular • Increased reticulocytes • Leukemia: • Blood loss • Malignant proliferation of immature cells • Increased reticulocytes • (MDS): • Cytopenia with hypercellular bone marrow

Bone Marrow Equipment Bone Marrow

Normal Aplastic

Aspirate Biopsy

4 Aplastic Anemia Bone Marrow Normal Bone Marrow Aspirate Aspirate

Erythroid (red cells) Myeloid (white cells)

Bone Marrow 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, -

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 • : 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 (>10% cells in one lineage) • RA = refractory anemia ƒ 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 • : 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

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