Hematologic Concepts I Winter 2024 Lecture PDF

Image from: "Red Blood cells" (Public Domain) by SciTechTrend. https://flic.kr/p/ENQRFe HEMATOLOGIC CONCEPTS 1 WINTER 2024 Jeanette Rodríguez, D.O. FM & OMT, ABFM and AOBFP Assistant Professor of Family Medicine Dr. Kiran C. Patel College of Osteopathic Medicine Nova Southeastern University Student...

Image from: "Red Blood cells" (Public Domain) by SciTechTrend. https://flic.kr/p/ENQRFe HEMATOLOGIC CONCEPTS 1 WINTER 2024 Jeanette Rodríguez, D.O. FM & OMT, ABFM and AOBFP Assistant Professor of Family Medicine Dr. Kiran C. Patel College of Osteopathic Medicine Nova Southeastern University Student Learning Objectives 1. Describe the overall organization of hematopathology and identify the associated erythrocyte lineage disorders. 2. Briefly discus the role of stem cells in with hematopoietic and lymphoreticular diseases. 3. List the components of the complete blood count (CBC) and its clinical application. 4. Discuss the value of the peripheral blood smear in the diagnosis of hematologic disorders and other diseases. 5. Define reticulocyte and discuss the clinical implication of the reticulocyte count. 6. Identify the laboratory tests that are used to assess anemia, polycythemia. 7. Define the hematologic diseases characterized by hyperproliferation, hypo-proliferation, and dilution. 8. Describe the diseases associated with normocytic/normochromic, microcytic/hypochromic, and macrocytic RBC indices. 2 Classification of Hematopathology Based on Lineages Erythrocyte Disorders This Lecture WBC Disorders Hematopathology Plasma Cell Disorders Platelet Disorders SLO # 1 3 Hematopoiesis: Blood Cell Differentiation and Lineages SLO # 1, 2 Image From: Blood Composition and Function. Medical Physiology: Principles for Clinical Medicine, 5e, 2017 4 Hematopoiesis: Blood Cell Differentiation and Lineages SLO # 1, 2 Image from: https://courses.lumenlearning.com/suny-ap2/chapter/production-of-the-formed-elements/ 5 Hematopathology: Classification of Disorders of RBC Erythrocytosis/ Polycythemia (too many cells) Anemia (too few cells) SLO # 7 6 Anemia: Etiology Decreased production Blood loss (hemorrhage) Increased destruction Anemia SLO # 7 7 This Photo by Unknown Author is licensed under CC BY-SA This Photo by Unknown Author is licensed under CC BY-SA-NC SLO # 7 This Photo by Unknown Author is licensed under CC BY-SA This Photo by Unknown Author is licensed under CC BY-SA 8 Enzyme Defects: Glucose-6-Phosphate Dehydrogenase Deficiency Pyruvate Kinase Deficiency Immune Mediated: Rh disease of the newborn Systemic Lupus Erythematosus Sickle Cell Anemia Thalassemia Infections: Membrane Defects: Hereditary Spherocytosis Elliptocytosis *Lectures to come Paroxysmal Nocturnal Hemoglobinuria Disorders of Hemoglobin Synthesis: SLO # 7 Acquired: Malaria and other parasitic infections 9 Anemia: Disorders of Decreased Production 1. Lack of raw materials: Iron deficiency anemia Anemia of chronic disease Folate deficiency anemia Vitamin B12 (cobalamin) deficiency anemia This Photo by Unknown Author is licensed under CC BY-SA 2. Problem with bone marrow: Myelophthisic anemia (marrow infiltration) Aplastic Anemia Pure Red Cell Dysplasia SLO # 7 This Photo by Unknown Author is licensed under CC BY 10 IL-6 Anemia: Disorders of Decreased Production 3. Other: Chronic inflammation Chronic diseases Ex: Anemia of Chronic Disease Chronic Disease Examples: SLO # 7 Image From: Management of Anemia of Inflammation in the Elderly Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Pathogenesis-of-anemia-ofinflammation-in-the-elderly-Abbreviations-EPOerythropoietin_fig2_232612155 [accessed 12 Feb, 2020] Diabetes mellitus Rheumatologic conditions (lupus, rheumatoid arthritis, psoriasis) Hypertension Coronary artery disease Congestive heart failure 11 Anemia of Chronic Disease (ACD) / Anemia of Inflammation (AI)/ Anemia of Chronic Inflammation (ACI) SLO #7 Secondary Iron Metabolism issues caused by inflammation Hepcidin = regulator of Fe metabolism (inhibitor) Image From:Ganz, Tomas. “Anemia of Inflammation.” New England Journal of Medicine, vol. 381, no. 12, Sept. 2019, pp. 1148–57, doi:10.1056/NEJMra1804281. https://www.nejm.org/doi/full/10.1056/NEJMra1804281 12 Polycythemia (Erythrocytosis): Etiology Relative Causes Absolute Causes Erythrocytosis Or Polycythemia SLO # 7 13 Etiology: Reduction of plasma volume leading to hemoconcentration Examples: Vomiting Diarrhea Polyuria SLO # 7 Image from: "Leaking" (CC BY 2.0) by nSeika. https://flic.kr/p/8NXLaA 14 SLO # 7 Primary: abnormal proliferation of myeloid stem cells with normal or low EPO levels  Ex: Polycythemia Vera Secondary: Proliferation of myeloid stem cells in the setting of elevated EPO levels Image From: Lippincott Illustrated Reviews: Integrated Systems, 1e, 2016 Renal System. Erythropoietin stimulation of erythrocyte maturation. Modified from Figure 44.17, 15 What are some causes of elevated EPO (i.e. secondary absolute causes)? Chronic lung disease Cyanotic heart disease High –altitude living EPO secreting tumors (renal cell carcinoma, hepatoma, cerebellar hemangioblastoma) Intake of EPO (athletes) Image From: Image from: https://www.webmd.com/drugs/2/drug-34/procrit-injection/details SLO # 7 16 This Photo by Unknown Author is licensed under CC BY-SA Into to the World Of Lab Tests SLO # 3, 6 17 Complete Blood Count (CBC) Definition: blood test performed with peripheral blood drawn that evaluates cells that circulate in blood Components: 1. White Blood Cell (WBC) count with or without a differential 2. Red Blood Cell (RBC) count 3. Hemoglobin (Hgb or Hb) 4. Hematocrit (Hct)  *Hgb/Hct sometimes referred to together as H/H 5. RBC indices: Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC), and Red Cell Distribution Width (RDW) 6. Platelet count with or without Mean Platelet Volume (MPV) and/or Platelet Distribution Width (PDW) SLO # 3, 6 18 Complete Blood Count (CBC): RBC Indices RBC Index Definition RBC Count # of red blood cells per cc of blood Hemoglobin Measure of amount of O2 carrying protein in RBCs Hematocrit (HCT) Measures volume percentage of RBC in blood MCH Measure of the amount of Hgb per cell MCHC Measure of the concentration of Hgb in each RBC MCV Measure of RBC size *DESCRIPTORS: MCHC: normochromic, hypochromic, hyperchromic MCV: normocytic, microcytic, macrocytic SLO # 3, 6 19 Complete Blood Count (CBC) Why is this test important? What components of the test would you use to evaluate?      SLO # 3, 6 Infection Anemia Malignancy Hereditable conditions Conditions of altered bone marrow production of cells 20 CBC w/ Diff SLO # 3, 6 Normal Ranges will vary based on lab, sex, age, and medical condition. 21 Peripheral Smear (normal) SLO # 4 Evaluates morphology 22 Heinz bodies Sickle Cell Bite cells Images from: Hematopoietic and lymphoid systems. Robbin’s Basic Pathology, 10e, 2018. Fig. 12.3 Fig 12.6 Peripheral Smear: Sickle cell SLO # 4 Peripheral Smear: G6PD Deficiency 23 Reticulocytes What are they?  Reticulocyte = large immature RBC How are they important?  ↑ counts indicate significant blood loss anemia or hemolytic anemia SLO # 5 Image from: https://courses.lumenlearning.com/suny-ap2/chapter/production-of-the-formed-elements/ 24 Iron Studies Iron Panel Tests Definition Ferritin Protein that stores iron. Transferrin Protein that transports iron in the blood “trans” TIBC Total Iron Binding Capacity; how much Fe can be bound to transferrin Iron SLO # 6 25 Iron Studies Iron test Serum Iron Serum Ferritin TIBC (Transferrin Saturation) Iron Saturation % Disease Iron Deficiency Anemia ↓ ↓ ↑ ↓ Anemia of Chronic Disease ↓ NL or ↑ ↓ NL or ↓ Thalassemia ↑ ↑ ↓ ↑ Sideroblastic ↑ ↑ ↓ ↑ *Transferrin is reflected by TIBC in labs SLO # 6 % Transferrin Fe Saturation = (Fe/ TIBC) x 100 26 Image from: Le, Tao and Bhushan, Vikas. First Aid for the USMLE Step 1, 29E. New York, NY: McGraw-Hill; 2019. Hemoglobin Electrophoresis SLO # 3-8 27 Anemia Characterization Based on Morphology *Based on RBC indices SLO # 8 28 Hypochromic and Microcytic Hypochromic: less than normal amount of hemoglobin Normal RBC  Look at MCHC Microcytic: cells are smaller than usual  Look at MCV  MCV Range: < 80 fL Think: Hemoglobin problem Common Etiologies:  Iron Deficiency Anemia  Thalassemia  Anemia of chronic disease (* sometimes) SLO # 4, 8 Image From: Robbin’s Basic Pathology, 10e, 2018 RBC with microcytic anemia 29 Normocytic Normochromic Normochromic: normal hemoglobin concentration  Look at MCHC  MCHC Range: 30-34 Normocytic: cells are normal sized  Look at MCV  MCV Range: 80-100 fL Think: Not enough cells Common Etiologies:       SLO # 4, 8 Hereditary Spherocytosis Sickle Cell Disease Acute blood loss Myelofibrosis Anemia of chronic disease (*usually) Renal disease Image From: https://imagebank.hematology.org/image/3710/normochromic-normocytic-anemia--1 30 Macroytic Macrocytic: cells are larger than usual Hypersegmented Neutrophil  Look at MCV  MCV range: >100 fL Think: DNA problem Common Etiologies:  B12 Deficiency Anemia  Ex: Pernicious anemia, strict vegetarians  Folate Deficiency Anemia Image From: Robbin’s Basic Pathology, 10e, 2018 SLO # 4, 8 Macrocyte 31 Anemia Comparison Chart Characteristics SLO # 8 Type of Anemia Microcytic Normocytic MCV < 80 fL 80-100 fL Etiology Hemoglobin Problem Not Enough Cells Macrocytic >100 fL Defective DNA Synthesis 32 Putting it Together… SLO # 3-8 33 History Initial Evaluation of Anemia Physical Exam CBC with interpretation of indices Reticulocyte count SLO # 3-8 34 Additional Anemia Work-up (as needed) SLO # 3-8 This Photo by Unknown Author is licensed under CC BY Blood smear Iron/TIBC B12 level Folic acid level Bilirubin Hemoglobin electrophoresis Osmotic fragility test Bone marrow aspiration 35 Lecture References Berkowitz, A. Clinical Pathophysiology Made Ridiculously Simple, 1E. Miami, FL: MedMaster Inc; 2007 Ganz, Tomas. “Anemia of Inflammation.” New England Journal of Medicine, vol. 381, no. 12, Sept. 2019, pp. 1148–57, doi:10.1056/NEJMra1804281. https://www.nejm.org/doi/full/10.1056/NEJMra1804281 Sattar, Hussain A. Pathoma: Fundamentals of Pathology. Pathoma LLC; Jan 2021. Loscalzo, J., Fauci, A.S., Kasper, D.L., Hauser, S.L., Longo, D.L., Jameson, J.L., Harrison's Principles of Internal Medicine, 21e. New York, NY: McGrawHill; 2022. Rothenberg, M.A. Smith, S.G. Laboratory Tests Made Easy: A Plain English Approach, 2E. Eau Claire, WI: PESI Publishing & Media; 2014 36 Additional Student Resources Videos: How to Interpret RBC Indices (e.g. hemoglobin vs. hematocrit, MCV, RDW). By strong medicine: https://www.youtube.com/watch?v=d0GxAtkBrgQ Fe Studies. By Lecturio: https://www.youtube.com/watch?v=AzPqQo5ZzOo Iron Studies (part 1: Iron Absorption): https://www.youtube.com/watch?v=_CWMUt8Xi_Y Iron Studies (Part 2: Serum Fe, TIBC, ferritin& %Sat.): https://www.youtube.com/watch?v=FyqwhbqGjTY&t=27s Anemia of Chronic Disease: All you need to know. By Medicosis Perfectionalis. https://www.youtube.com/watch?v=k34oCxnynOA Iron Deficiency Anemia: All you need to know. By Medicos Perfectionalis. https://www.youtube.com/watch?v=nWHQRptC_9Q 37 Additional Student Resources Articles: Ganz, Tomas. “Anemia of Inflammation.” New England Journal of Medicine, vol. 381, no. 12, Sept. 2019, pp. 1148–57, doi:10.1056/NEJMra1804281. https://www.nejm.org/doi/full/10.1056/NEJMra1804281 Langan, R.C., Goodbred, A.J., Vitamin B12 Deficiency: Recognition and Management. Am Fam Physician. 2017 Sep 15;96(6):384-389. Books: Kumar, V., Abbas, A., Aster, J., Robbin’s Basic Pathology, 10e. Philadelphia, PA: Elsevier; 2018. Le, Tao and Bhushan, Vikas. First Aid for the USMLE Step 1, 32E. New York, NY: McGraw-Hill; 2022. Rothenberg, M.A. Smith, S.G. Laboratory Tests Made Easy: A Plain English Approach, 2E. Eau Claire, WI: PESI Publishing & Media; 2014 Sattar, Hussain A. Pathoma: Fundamentals of Pathology. Pathoma LLC; Jan 2021 38 Any Questions? This Photo by Unknown Author is licensed under CC BY-NC Additional questions will also be answered on the Canvas discussion board. 39