HEMATL1 - PRELIMS - LEC.pdf

HEMATOLOGY1 3rd Year - 1st Semester | SY 2024-2025 SEPHYTU INTRODUCTION TO HEMATOLOGY 3. Maintenan...

HEMATOLOGY1 3rd Year - 1st Semester | SY 2024-2025 SEPHYTU INTRODUCTION TO HEMATOLOGY 3. Maintenance of constant body temperature o Circulating blood minimizes variations in local temperature 4. Defense o Phagocytosis (define this term) o Blood contains proteolytic enzymes and antibodies that help destroy foreign bodies. CHARACTERISTICS OF BLOOD Physical Characteristics of Whole Blood Color: Normally red as imparted by hemoglobin. Viscosity: 3 - 5 x more viscous than water Circulates in liquid state Coagulates between 5 – 10 minutes after removal from the body pH: 7.35 – 7.45 Sp. Gravity (whole blood): 1.048 – 1.066 o Serum: 1.026 – 1.031 o RBC: 1.092 – 1.095 Volume: 5 – 6 liters (7 - 8% of total body wt) o Males : 76 ml/kg body wt o Females: 68 ml/kg body wt NORMAL COMPOSITION OF BLOOD LIQUID PORTION Plasma or Serum: 55% of the total blood volume o 91 – 92% by weight is water o 6 – 7% by weight includes plasma proteins and other substances like vitamins, carbohydrates, etc. Plasma proteins o albumin: 4% (helps maintain osmotic pressure) o globulin: 2.7% ▪ alpha globulins ▪ beta globulin ▪ gamma globulin o fibrinogen: 0.3% Plasma: Liquid portion of an unclotted blood BLOOD Serum: Liquid portion of clotted blood. PUSC Nutritive fluid that circulates in the vascular system SOLID PORTION FUNCTIONS OF BLOOD: 45% of the of the total blood volume 1. Transport of: RBC (erythrocytes, erythroplastids, normocytes) o gases to facilitate gas exchange (O2 and CO2) WBC (leukocytes; leukoplastids) o products of digestion to tissues where they Platelets (thrombocytes; thromboplastids) will be metabolized or assimilated o Hemoconia o waste products of catabolism to the excretory ▪ small refractive colorless particles in organs the blood that are probably granules o hormones and other endocrine secretions from blood cells or minute fat that regulate cell functions globules. 2. Buffering action GASEOUS PORTION o Blood assists in the preservation of an almost Portion where exchange between O2 and CO2 for neutral reaction in the tissues normal respiration occurs. o Helps maintain normal water balance and fluid distribution Papasa sa prelims | 1  SEPHYTU HEMATOPOIESIS o HbA2 2 Alpha & 2 Delta (TaDA) Blood cells produce: Continuous, regulated process of blood cell o All cells are being produce production that includes cell renewal, proliferation, Duration (start-end): differentiation, and maturation. o Start: 5th Age of gestation o End: Life time TYPES *** Measurable levels of Hb Feature Primitive Definitive B. EXTRAUTERINE PHASE Hematopoiesis Hematopoiesis Early embryonic Embryogenesis → I. MYELOID/MEDULLARY PHASE Timing development Lifetime Postpartum Bone Marrow Function Bone marrow (and o After 3 weeks after birth, Yolk sac, fetal Location fetal spleen/lymph o Bone Marrow - sole site of hematopoiesis liver, placenta nodes) Primitive Location of Red Marrow Cell Types erythrocytes, early Mature Blood Cells o Children: progenitors ▪ Skull It does involve ▪ Clavicle your Involves hematopoietic ▪ Ribs Stem Cells hematopoietic stem cells (HSCs) ▪ Vertebrae stem cells (HSCs) ▪ Pelvis Highly regulated by ▪ Long bones Regulation Less regulated cytokines and factors o Adults (18+ years): ▪ Ribs Site of hematopoiesis: ▪ Sternum Ribs, ▪ Skull sternum, ▪ Scapula skull, ▪ Vertebrae scapula, ▪ Pelvic Bones vertebrae, ▪ Proximal ends of the long bones pelvic bones, II. EXTRAMEDULLARY HEMATOPOIESIS proximal ends of the long bones Normal Occurrence: PHASES OF HEMATOPOIESIS o Liver and spleen o Especially during fetal development A. INTRAUTERINE PHASE Pathological Conditions: o Occur when your bone marrow is unable to produce enough RBC 1. MESOBLASTIC OR MEGALOBLASTIC PHASE Function: Chief Site: YOLK SAC o Takes place outside the Bone Marrow and it Hemoglobin present: can either physiologic / pathologic o Gower I: 2 Zeta & 2 Epsilon (ONEZ) o Gower II: 2 Alpha & 2 Epsilon (TAE) IDIOPATHIC - unknown source of the infection o Portland: 2 Zeta & 2 Gamma (POGZ) Blood cells produced C. ADULT HEMATOPOIETIC TISSUE o Primitive Erythroblast Duration (start-end): o Start: 19th - 20th Day 1. BONE MARROW o End: 8 - 12th week 1.a) Red Marrow: Function: 2. HEPATIC PHASE o Hematopoietically active, blood cell Chief Site: LIVER (main organ), Spleen production Hemoglobin present: Age: o Hb F (Major): 2 Alpha & 2 Gamma (FAG) o predominantly infancy or childhood o HbA1 Structure: o HbA2 o contains your extramedullary cords with Blood cells produced: stem cell progenitors o Erythrocytes Duration (start-end): o Start: 5th - 7th week Cell locations o End: 1st and 2nd week after birth *** Detectable levels of hemoglobin o Normoblasts: 3. MYELOID / MEDULLARY PHASE ▪ develops in cluster near the outer surface of vascular sinuses Chief Site: Bone Marrow o Megakaryocytes: Hemoglobin present: ▪ located at the vascular walls of o HbA1 (major): 2 Alpha & 2 Beta (BAO) sinuses Papasa sa Prelims | 2  SEPHYTU o Immature myeloid cells: States that there are two to three cell origins. ▪ deep within the cords There is a separate and distinct stem cell compartment 1.b) Yellow Marrow Sub-theories: Function: o a. Dualistic o Hematopoietically INACTIVE ▪ Lymphoblast → lymphocytes o Doesn’t produce, it needs something to ▪ Myeloblast → granulocytes, stimulate the production monocytes, and megakaryocytes o Primarily composed of ADIPOCYTES (Fat ▪ Pronormoblast → red blood cells cells) o b. Trialistic Age: ▪ Reticuloendothelial cells give rise o Start at the age of 5 to monocytes Process: ▪ Can be find around the body o RETROGRESSION ▪ The process of replacing the active COMPLETE THEORY marrow by adipocytes believes that there is a separate stem cell for each ▪ The process of red marrow cell series converting into yellow marrow Prescence of stem cell for each of several cell series Under the physiologic stress, the yellow marrow will Example: revert back to active marrow o Myeloblasts → lymphocytes o Lymphoblasts → lymphocytes 2. LIVER STEM CELLS PRODUCED BY THE BONE MARROW primary site of the hematopoiesis during the hepatic phase of hematopoiesis HEMOHISTIOBLAST: one single fixed multipotent stem cell that gives rise to 3. SPLEEN tissue and to blood cells. Splenic culling and pitting o Pitting: PLURIPOTENT STEM CELL (PPSC) - Splenic macrophage Present in small numbers (constant) in the BM - removed → damage RBCs Not morphologically identifiable - Removal of the inclusion bodies of RBC in the spleen Has the ability to reproduce and differentiate - Inclusion bodies: RBC that have components inside o Culling: CFU-S - aged RBCs senescent (old: above 120 days) and Colony Forming unit - spleen damaged RBC CLP (Common Lymphoid Progenitor): Stores about 1/3 (one-third) of platelets o lymphocytes, NK, Dendritic cells 2/3: Circulation o CLiP LaND (Cleve land) CMP (Common Myeloid Progenitor): Zones o Granulocytic, erythrocytic, monocytic, o Marginal Zone: megakaryocytic (GEMM) - It has macrophage and specialized B Cells o White Pulp: GROWTH FACTORS IN BLOOD CELL PRODUCTION - Contains lymphocytes, macrophages and dendritic cells Growth Factors: o Red Pulp: o Proteins that regulate blood cell production, - Filtering blood including cytokines and hormones. o Kit Ligand (KL): 4. LYMPH NODE ▪ "Stem cell factor" or "steel factor." Germinal Centers: Stimulates the development of o Site of the formation of your new myeloid, erythroid, and lymphoid lymphocytes progenitors. Immunoglobulin Processing: o Flt-3 Ligand (FL): o Involves in the production of specific ▪ Involved in the regulation of antibodies primitive progenitor cells. 5. THYMUS Function o Develop T-cells THEORIES ON THE ORIGIN OF BLOOD CELLS MONOPHYLETIC (UNITARY) THEORY blood cells come from one stem cell which is totipotent, giving rise to any series of cell types Mono = one stem cell POLYPHYLETIC THEORY: Papasa sa Prelims | 3  SEPHYTU THE RELEASE OF BLOOD CELLS FROM THE BONE MARROW INVOLVES DIFFERENT MECHANISMS: RED BLOOD CELLS (RBCS): Their release is stimulated by erythropoietin, hypoxia, the maturation stage of the cells (such as reticulocytes), and the pressure from growing cells within the marrow. WHITE BLOOD CELLS They exit the bone marrow via chemotaxis. PLATELETS: They are released into circulation through a process called platelet shedding. Changes during normal blood cell maturation CYTOKINES Cell Size Decrease with the exception of megakaryocyte small protein that helps cells to communicate with Nuclear/Cytoplasmic (N/C) Decreases each other, often regulating immune responses and Ratio cell growth Nucleus Cytokine List of Cytokines and Growth Factors a. Size Decrease IL-2 Responsible for growth of T cells, B cells b. Nuclear Chromatin Coarse → Clumped → and NK cells Granular → Fine IL-3 Multi-lineage stimulating factor c. Number of Nucleoli Decreases IL-4 T Cells, B cells and mast cells d. Staining Reddish to bluish purple IL-6 Stems cells, but also B cells Cytoplasm IL-7 Pre-B cells, T cells and Early granulocytes a. Basophilia Gradually decreases IL-11 Megakaryocyte GM-CSF Granulocyte, Macrophage, Fibroblast, and b. Amount/Size Increases endothelial Cells c. Cytoplasmic Produce in some cells EPO Red cells progenitors Constituents Criteria for Assessing Cell HEMATOPOIETIC HORMONES Maturity a. Cell Size Evaluate the maturation ERYTHROPOIETIN b. Nuclear Maturation The best criteria for checking produced by the kidneys (90%) and the liver (10%) cell age Functions: c. Cytoplasmic Access cellular maturation o prevents the apoptosis of erythroid Maturation/Changes precursors Cell Maturation Details o Stimulates Hb synthesis a. Blast Cells No granules, large nucleus, o serves as differentiation factor causing the small cytoplasm CFU-E to differentiate into pronormoblast b. Cytoplasm Color Blue - younger cells THROMBOPOIETIN c. Chromatin Heavier and darker color Also known as mpL kit ligand d. Nucleoli Disappear in mature cells Synthesized by the liver e. Granules a. Neutrophil Less prominent and smaller ANTIGENIC MARKERS b. Basophil with age CD 34 Stem cell CD 2 Lymphoid, pan T cells marker CD 3 c. Eosinophil CD 33 Pan myeloid CD 3 Helper/inducer T cells e. Specific Granules cells CD 13 Pan myeloid CD 8 Suppressor/cytotoxic Synchronous Asynchronous T cells Maturation Maturation CD 11c monocytes CD 10, Lymphoid, pan B cells Definition Coordinated and Abnormal CD 14 CD19, parallel maturation with CD 20 development of differing rates for CD 17 erythroid CD 16, NK cells nucleus and nucleus and CD56 cytoplasm cytoplasm Type Physiologic - Pathologic - disease Normally occur occuring Papasa sa Prelims | 4  SEPHYTU Cell Nucleus and Nucleus and HEMATOPOIETIC Maturation cytoplasm mature cytoplasm mature at simultaneously different rates ERYTHROPOIESIS Nuclear- Changes in a Mature at different Process of the RBC production Cytoplasmic coordinated rate Takes about 3-5 days for the production of (N/C) Ratio manner with cell reticulocyte from pronormoblast maturation Appearance Consistent and Discrepancies in cell Normoblastic Rubriblastic Erythroblastic balance changes in component cell components maturation Examples Regular Abnormalities such Pronormoblast Rubriblast Proerythroblast development of as in certain Basophilic Basophilic healthy blood cells leukemias Prorubricyte normoblast erythroblast Polychromatophilic Polychromatophilic DEFINITIONS Rubricyte normoblast erythroblast Orthochromic Meta Orthochromic PLURIPOTENTIAL normoblast Rubricyte erythroblast This means having the capacity to differentiate into Polychromatophilic Polychromatophilic Reticulocyte many different cell types. In the context of erythrocyte erythrocyte hematopoiesis, it specifically refers to stem cells that Mature can give rise to all the various types of blood cells. Erythrocyte Erythrocyte eryhrocyte Cell Stage Characteristics Cytoplasm Chromatin Nucleoli N:C Notes Ratio Deeply Earliest basophilic Takes ~3 days to develop recognizable 8:1 Pronormoblast (attracted to Fine 1-2 into orthochromic normoblast. red blood cell (High) acidic dye) Globin production begins. precursor Non-granular Nuclear Last stage with nucleolus. Basophilic chromatin Intensely Hemoglobin synthesis is Slightly Coarse Not visible 6:1 Normoblast becomes more basophilic detectable, however in EM clumped. only Characterized by a muddy, First visible hemoglobin gray-blue Polychromatophilic Blue-grey to Knotted or synthesis. appearance due None 4:1 Normoblast pink-grey clumped Last stage capable of to mixed pink mitosis. and basophilic stain Nucleus is Small pyknotic Nearly complete Pink cytoplasm Orthochromic tightly (Ejected hemoglobin production. “Ortho” – color None 2:1 Normoblast condensed nucleus) Mitotically inactive. change (pyknotic). nucleus Last stage with a nucleus. Pink to slightly pinkish grey Reticulocyte cytoplasm, Polychromatophilic when stained Small pyknotic anucleated Last stage capable of contains fine Erythrocyte with supravital nucleus Absent hemoglobin synthesis. basophilic stain. remnants of RNA Salmon pink or Erythrocyte red with pale Absent Normal life span: 120 days central pallor Papasa sa Prelims | 5  HEMATOLOGY1 3rd Year - 1st Semester | SY 2024-2025 SEPHYTU FACTORS AFFECTING RBC PRODUCTION PROTEIN Growth Factors; Hormones (Androgenic Hormones and Necessary for hemoglobin production. Progtaglandins) Erythropoietin (EPO): COBALT o produced by the kidney due to hypoxia (low Part of vitamin B12, supports RBC production level of oxygen) similarly to EPO. G-CSF and SCF – supports overall production Other Hematopoietic Growth Factors FOLIC ACID Androgenic Hormones: Vital for RBC formation, also known as citrovorum o Testosterone factor or folinic acid. ▪ Stimulate EPO and increase the sensitivity of RBC progenitor cell VITAMIN B12 Prostaglandins: Essential for RBC production, also known as o Modulate the effect of EPO cyanocobalamin. IRON VITAMIN B6 (PYRIDOXINE) Essential for hemoglobin synthesis; body contains 3-5 Important for RBC production. grams. Absorbed from the intestines, transported in plasma, and used in the bone marrow. About 55% of VITAMIN C stored iron is used for RBC production. Enhances effective RBC production COPPER Present in small amounts (100-150 mg), crucial for iron metabolism and hemoglobin formation. Exists as serum ceruloplasmin and erythrocuprein. RBC METABOLIC PATHWAY: Pathway Function Key Components - Anaerobic glycolysis Embden-Meyerhof Pathway - ATP production - Supplies 90-95% of ATP - Generates G6PD and glutathione - G6PD Hexose Monophosphate Shunt - Prevents oxidative denaturation of - Glutathione hemoglobiin - Maintains iron in hemoglobin in a - Reduces methemoglobin to functional Methemoglobin Reductase Pathway reduced (ferrous) state for oxygen hemoglobin transport - Generates 2,3-DPG, which helps Rapoport-Luebering Shunt regulate oxygen release from - 2,3-DPG hemoglobin Loss of Loss of Decrease Decrease Decrease nucleoli Ribosome in rRNA in acidity Basophilia Papasa sa prelims | 6  SEPHYTU GRANULOPOIESIS GRANULOPOIESIS STAGES Includes: Neutrophils, Eosinophils, and Basophils Progenitor cells: o CFU-G: Neutrophils o CFU-EO: Eosinophils o CFU-Baso: Basophils They share the same maturation but varies in morphologic changes STAGE NOTES CYTOPLASM NUCLEUS NUCLEOLI N/C RATIO Round or Earliest recognizable Basophilic and scanty slightly oval; MYELOBLAST 2–5 4:1 blast No visible granules Fine and Lazy chromatin Basophilic and abundant; Oval to round. Primary granules slightly coaster PROMYELOCYTE 2–3 3:1 – 2:1 appear chromatin (Azurophilic granules/ patten Non-specific granules) Moderate amount with specific granules Oval to round. Dawn of MYELOCYTE Secondary granules Coarse Neutrophils appear (specific chromatin granules) Indented / kidney bean Moderate to abundant Peanut shape with specific granules METAMYELOCYTE Aka. Juvenile cell shaped. Tertiary granules Coarser and appear clumped chromatin Stab/Stamm cells. Elongated or Indentation of Specific granules band shaped. nucleus. is higher Secretory granules (Sausage) BAND CELLS than 50x width First immature WBC Coarse and Youngest cell in to be release in the clumped granulocytic series in circulation. chromatin Peripheral blood MATURE GRANULOCYTE Granules: o Primary (azurophilic) granules (MCADEP) Myeloperoxidase Cathepsin Acid Beta-glycerophosphate Defensins Elastase Proteinase o Secondary granules (LL) Lactoferrin Lipocalin NEUTROPHIL o Tertiary Granules (LA) Lysozyme + Acetyltransferase Cytoplasm: grainy appearance (Pink/ rose pink violet o 2nd and 3rd (BGC) granules) Gelatinase o Can be segmented Collagenase Nucleus: 3-4 lobes B2-microglobulin Papasa sa Prelims | 7  SEPHYTU MOST COMMON WBC in normal peripheral blood Functions: Two forms: Segmenter and Bands o Phagocytosis o Inflammatory and hypersensitivity FERRATA CELLS: o Defense against parasitic activity o Tissue Neutrophils o Inactivate substances produced by basophils o Associated with sub-acute bacterial and mast cells/prevent basophil and mast cell endocarditis (SBE) granulation o Destroy larval stages of helminths BARR BODIES o Stores plasminogen o Represent the second X chromosome o “Drumstick” Secondary granules stains highly in eosin o Found in females Myelocyte Stage: o Distinguishable because of granules POOLS OF NEUTROPHILS IN THE BONE MARROW containing major basic protein (MBP) a. Mitotic Proliferating pool Important Major Products - Myeloblast, Promyelocyte, myelocyte o MBP – damaging parasite - Cells undergoing cell division o Charcot-Leyden Crystals ▪ Hexagonal b. Storage/ maturation pool ▪ During parasitic and hypersensitivity - Metamyelocyle, Bands, Segmented neutrophils Life span: 18 hours half-life in blood - Cells no longer undergoing cell division but Inactivate by releasing enzyme and protein progressively maturing BASOPHILS POOLS OF NEUTROPHILS IN THE CIRCULATION (50:50) a. Circulating Pool - circulation Cytoplasm: with few, large and densely stained, dark b. Marginating Pool - adhere all endothelial lining that purple to blue black granules can be formed into marginating tool Nucleus: round, indented, band or bilobed with Once the marginal pool was detached, the WBC will SMUDGED chromatin pattern increase will lead to physical and emotional stress Granules - Diapedesis o Heparin o Immigration – redistributing itself by o Serotonin going near the vascular lining o Peroxidase o WBC leaving the circulation o Histamine - Chemotaxis Function: o Directional movement o Mediate inflammatory response and o Chemotaxis substance - Chemical immediate hypersensitivity reaction Stimuli o Delayed hypersensitivity reaction Basophils o Neutrophil will leave the bone and mast cells have a specific receptor for IgE marrow o Water soluble, - Respiratory burst o Less than 1% in the blood o Release of reactive oxygen o Can help kill and digest living MAST CELLS bacteria Mesenchymal origin Functions: Phagocytosis Larger in size o Random and directional movement Smaller but more numerous granules Life span 9-10 days Less water soluble 7 hours in the blood then migrates to the tissue Same function with basophils First one to arrive in infection site Contains proteolytic enzymes and serotonin, histamine and heparin EOSINOPHILS Cytoplasm: red-orange refractile granules Nucleus: band or bilobed Coarse and clumped chromatin pattern Granules: o Histamines o Peroxidase o B-glucuronidase o Arylsulfatase o ACP o Phospholipase, o Ribonuclease o Cathepsin Life span: 18 hours half-life in blood to 6 days in tissues Papasa sa Prelims | 8  SEPHYTU MONOPOIESIS MONOBLAST Cytoplasm: Basophilic cytoplasm Nucleus: Round Nucleoli: 1 – 2 N/C Ratio: 4:1 – 3:1 MONOCYTE PROMONOCYTE Main function: PHAGOCYTOSIS FIRST RECOGNIZABLE in bone marrow Slightly immature cells whose ultimate goal is to enter Cytoplasm: Blue grey the tissues and mature into macrophages N/C Ratio: 3:1 – 2:1 → Type of white blood cells that play a crucial role in your immune system They are the LARGEST WHITE BLOOD cells and can differentiate into macrophages and dendritic cells Develop similar to neutrophil development because the MONOCYTE 2-cell type share GMP (colony forming unit) Cytoplasm: Abundant, Blue-grey and ground glass, Monocyte are larger than neutrophil Many fine azurophilic granules (primary granules) Nucleus: Round, Kidney shaped, may show slight lobulation or may be folded, horseshoe or tulip, brain or kidney With fine lacy chromatin Lifespan: o Circulation: 12 hours o Tissues to macrophage Granules (BLLAP) o B-glucuronidase Makes up between 2% and 10% of circulating o Lysozyme leukocytes o Lipase 96 – 1100 monocytes per microliter o ACP Size: 15 – 20 um o Peroxidase Chromatin: Lacelike Nucleus: Horseshoe or tulip shape Cytoplasm: Blue-gray with fine azure granules or ground glass appearance STAGES OF MATURATION: MONOCYTOPOIESIS MACROPHAGE Tissue counterpart of the blood monocyte Larger than monocyte Papasa sa Prelims | 9  SEPHYTU FUNCTION Phagocytosis With receptor for the FC portion of IgG and C3 complement Cellular and Humoral activity Remove damaged and old cells Can kill malignant cells and tumor cells Handle and process antigen and present them to lymphocytes Participates in iron metabolism NON-A NON-B POPULATION LYMPHOPOIESIS NK CELLS SITE OF LYMPHOPOIESIS Recognition & lysis of tumor cells 1. Primary Lymphoid Organ (PLO) Regulation of hematopoiesis and immune regulation o Bone marrow: B lymphocytes 10-20% (BB) o Thymus : T lymphocytes 60-80% (TT) KILLER CELLS Destruction of Ab-coated cells 2. Secondary Lymphoid Organ (SLT) o Spleen and Lymph Nodes PLASMA CELL MATURATION Function: Immune response 1. Plasmablast Serves as a "marker cell" for estimating the size of 2. Proplasmacyte surround cells 3. Plasmacyte T cell: most small lymphocytes B cell: Most large lymphocytes PLASMA CELLS Life span: several months to years 8 – 20 um in diameter Oval/egg-shaped cell STAGES OF LYMPHOCYTE Deeply basophilic cytoplasm Cartwheel pattern Large well defined hof (perinuclear halo) Eccentric nucleus Chromatin is condensed and coarse MEGAKARYOCYTE The nucleus of megakaryocyte increases as it matures PLATELETS/THROMBOCYTES 2 - 4 um in diameter Light blue to purple andvery granular Common Lymphoid Progenitor Life span: 8 - 11 days Daily turnover: 35 x 109/L (+/- 4.3) Maturation: about 5 days Distribution: o Spleen 1/3 o Circulation 2/3 MEGAKARYOCYTE (STEININGER) Papasa sa Prelims | 10  SEPHYTU MEGAKARYOCYTE LINEAGE COMMITED PROGENITORS BFU-MEG: least mature, capable of mitosis CFU-MEG: intermediate, capable of mitosis LD-CFU-MEG: most mature, ENDOMITOSIS Endomitosis o maturation is marked by a mysterious form of mitosis that lacks telophase and cytokinesis o Multiple mitotic division but without cell division o Production of Giant nucleated and polyploid cell Divided into four stages Least mature to mature 1. Megakaryoblast 2. Promegakaryocyte 3. Megakaryocyte 4. Metamegakaryocyte RODAKS 3 Stages only PLATELET SHEDDING Papasa sa Prelims | 11