DOCSLIB.ORG

TR-507: Vanadium Pentoxide (CASRN 1314-62-1) in F344/N Rats

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
TR-507: Vanadium Pentoxide (CASRN 1314-62-1) in F344/N Rats NTP TECHNICAL REPORT ON THE TOXICOLOGY AND CARCINOGENESIS STUDIES OF VANADIUM PENTOXIDE (CAS NO. 1314-62-1) IN F344/N RATS AND B6C3F1 MICE (INHALATION STUDIES) NATIONAL TOXICOLOGY PROGRAM P.O. Box 12233 Research Triangle Park, NC 27709 December 2002 NTP TR 507 NIH Publication No. 03-4441 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health FOREWORD The National Toxicology Program (NTP) is made up of four charter agencies of the U.S. Department of Health and Human Services (DHHS): the National Cancer Institute (NCI), National Institutes of Health; the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health; the National Center for Toxicological Research (NCTR), Food and Drug Administration; and the National Institute for Occupational Safety and Health (NIOSH), Centers for Disease Control and Prevention. In July 1981, the Carcinogenesis Bioassay Testing Program, NCI, was transferred to the NIEHS. The NTP coordinates the relevant programs, staff, and resources from these Public Health Service agencies relating to basic and applied research and to biological assay development and validation. The NTP develops, evaluates, and disseminates scientific information about potentially toxic and hazardous chemicals. This knowledge is used for protecting the health of the American people and for the primary prevention of disease. The studies described in this Technical Report were performed under the direction of the NIEHS and were conducted in compliance with NTP laboratory health and safety requirements and must meet or exceed all applicable federal, state, and local health and safety regulations. Animal care and use were in accordance with the Public Health Service Policy on Humane Care and Use of Animals. The prechronic and chronic studies were conducted in compliance with Food and Drug Administration (FDA) Good Laboratory Practice Regulations, and all aspects of the chronic studies were subjected to retrospective quality assurance audits before being presented for public review. These studies are designed and conducted to characterize and evaluate the toxicologic potential, including carcinogenic activity, of selected chemicals in laboratory animals (usually two species, rats and mice). Chemicals selected for NTP toxicology and carcinogenesis studies are chosen primarily on the bases of human exposure, level of production, and chemical structure. The interpretive conclusions presented in this Technical Report are based only on the results of these NTP studies. Extrapolation of these results to other species and quantitative risk analyses for humans require wider analyses beyond the purview of these studies. Selection per se is not an indicator of a chemical’s carcinogenic potential. Details about ongoing and completed NTP studies are available at the NTP’s World Wide Web site: http://ntp-server.niehs.nih.gov. Abstracts of all NTP Technical Reports and full versions of the most recent reports and other publications are available from the NIEHS’ Environmental Health Perspectives (EHP) http://ehp.niehs.nih.gov (800-315-3010 or 919-541-3841). In addition, printed copies of these reports are available from EHP as supplies last. A listing of all the NTP Technical Reports printed since 1982 appears on the inside back cover. NTP TECHNICAL REPORT ON THE TOXICOLOGY AND CARCINOGENESIS STUDIES OF VANADIUM PENTOXIDE (CAS NO. 1314-62-1) IN F344/N RATS AND B6C3F1 MICE (INHALATION STUDIES) NATIONAL TOXICOLOGY PROGRAM P.O. Box 12233 Research Triangle Park, NC 27709 December 2002 NTP TR 507 NIH Publication No. 03-4441 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health 2 CONTRIBUTORS National Toxicology Program NTP Pathology Working Group Evaluated and interpreted results and reported findings Evaluated slides and prepared pathology report on rats (July 27, 2000) N.B. Ress, Ph.D., Study Scientist M.T. Butt, D.V.M., Chairperson J.H. Roycroft, Ph.D., Study Scientist Pathology Associates International D.W. Bristol, Ph.D. A.E. Brix, D.V.M., Ph.D. J.R. Bucher, Ph.D. Experimental Pathology Laboratories, Inc. J.R. Hailey, D.V.M. D. Dungworth, D.V.M. J.K. Haseman, Ph.D. University of California, Davis R.A. Herbert, D.V.M., Ph.D. J. Everitt, D.V.M. R.R. Maronpot, D.V.M. Chemical Industry Institute of Toxicology D.P. Orzech, M.S. G.P. Flake, M.D. S.D. Peddada, Ph.D. National Toxicology Program J.R. Hailey, D.V.M. G.N. Rao, D.V.M., Ph.D. National Toxicology Program C.S. Smith, Ph.D. R.A. Herbert, D.V.M., Ph.D. G.S. Travlos, D.V.M. National Toxicology Program K.L. Witt, M.S., ILS, Inc. M.P. Jokinen, D.V.M. Pathology Associates International IITRI R.R. Maronpot, D.V.M. Conducted 16-day and 3-month studies National Toxicology Program and evaluated pathology findings K. Nikula, D.V.M., Ph.D. Monsanto C. Aranyi, M.S., Principal Investigator A. Nyska, D.V.M. D.T. Kirkpatrick, Ph.D. National Toxicology Program R.E. Long, D.V.M. R.A. Renne, D.V.M. N. Rajendran, Ph.D. Battelle Toxicology Northwest A. Snelson, Ph.D. Evaluated slides and prepared pathology report on mice M.J. Tomlinson, D.V.M., Ph.D. (August 21, 2000) S.C. Vana, B.S. M.P. Jokinen, D.V.M., Chairperson Pathology Associates International Battelle Toxicology Northwest D. Dixon, D.V.M., Ph.D. Conducted 16-day special studies and 2-year studies National Toxicology Program and evaluated pathology findings J. Everitt, D.V.M. Chemical Industry Institute of Toxicology B.J. Chou, D.V.M., Ph.D., Principal Investigator G.P. Flake, M.D. J.A. Dill, Ph.D., Principal Investigator National Toxicology Program M.L. Clark, M.S.E. J.R. Hailey, D.V.M. S.R. Baum, B.S. National Toxicology Program K.M. Lee, Ph.D. R.A. Herbert, D.V.M., Ph.D. R.A. Miller, D.V.M., Ph.D. National Toxicology Program E.W. Morgan, M.S.E. M. Jayo, D.V.M., Ph.D., Observer R.A. Renne, D.V.M. Pathology Associates International R.A. Miller, D.V.M., Ph.D. Battelle Toxicology Northwest Experimental Pathology Laboratories, Inc. A. Nyska, D.V.M. Provided pathology quality assurance National Toxicology Program K. Ozaki, D.V.M., Ph.D., Observer J.F. Hardisty, D.V.M., Principal Investigator National Toxicology Program A.E. Brix, D.V.M., Ph.D. J.C. Seely, D.V.M. J.C. Seely, D.V.M. Experimental Pathology Laboratories, Inc. Vanadium Pentoxide, NTP TR 507 3 Dynamac Corporation Biotechnical Services, Inc. Prepared quality assurance audits Prepared Technical Report S. Brecher, Ph.D., Principal Investigator S.R. Gunnels, M.A., Principal Investigator L.M. Harper, B.S. Analytical Sciences, Inc. D.C. Serbus, Ph.D. Provided statistical analyses B.F. Hall, M.S. R.A. Willis, B.A., B.S. P.W. Crockett, Ph.D., Principal Investigator P.A. Yount, B.S. L.J. Betz, M.S. M.R. Easterling, Ph.D. K.P. McGowan, M.B.A. J.T. Scott, M.S. 4 CONTENTS ABSTRACT . 7 EXPLANATION OF LEVELS OF EVIDENCE OF CARCINOGENIC ACTIVITY . 12 TECHNICAL REPORTS REVIEW SUBCOMMITTEE . 13 SUMMARY OF TECHNICAL REPORTS REVIEW SUBCOMMITTEE COMMENTS . 14 INTRODUCTION . 17 MATERIALS AND METHODS . 27 RESULTS . 45 DISCUSSION AND CONCLUSIONS . 93 REFERENCES . 99 APPENDIX A Summary of Lesions in Male Rats in the 2-Year Inhalation Study of Vanadium Pentoxide . 109 APPENDIX B Summary of Lesions in Female Rats in the 2-Year Inhalation Study of Vanadium Pentoxide . 149 APPENDIX C Summary of Lesions in Male Mice in the 2-Year Inhalation Study of Vanadium Pentoxide . 185 APPENDIX D Summary of Lesions in Female Mice in the 2-Year Inhalation Study of Vanadium Pentoxide . 225 APPENDIX E Genetic Toxicology . 263 APPENDIX F Cardiopulmonary Physiology Studies . 269 APPENDIX G Clinical Pathology Results . 275 APPENDIX H Organ Weights and Organ-Weight-to-Body-Weight Ratios . 283 APPENDIX I Reproductive Tissue Evaluations and Estrous Cycle Characterization . 289 APPENDIX J Immunotoxicology Studies . 293 APPENDIX K Tissue Burden Results . 299 APPENDIX L Chemical Characterization and Generation of Chamber Concentrations . 313 Vanadium Pentoxide, NTP TR 507 5 APPENDIX M Ingredients, Nutrient Composition, and Contaminant Levels in NTP-2000 Rat and Mouse Ration . 329 APPENDIX N Sentinel Animal Program . 333 APPENDIX O Molecular Oncology Studies . 337 6 Vanadium Pentoxide, NTP TR 507 SUMMARY Background Vanadium pentoxide is used in the production of vanadium and steel alloys and is emitted by burning fossil fuels. Exposure to vanadium pentoxide occurs during the cleaning of oil-fired boilers and furnaces. Methods We exposed groups of 50 male and 50 female rats to atmospheres containing aerosols of 0.5, 1, or 2 mg of vanadium pentoxide particles per cubic meter of air. We also exposed groups of 50 male and 50 female mice to atmospheres containing 1, 2, or 4 mg vanadium pentoxide per cubic meter. Animals were exposed six hours per day, five days per week for two years. Tissues from more than 40 sites on each animal were examined. Results Male rats exposed to vanadium pentoxide had greater than normal incidences of lung neoplasms, and some lung tumors also occurred in exposed female rats. Other lesions including inflammation, fibrosis, and hyperplasia also occurred in the respiratory tract (nose, larynx, and lung) of male and female rats. These lesions were more severe at higher vanadium pentoxide concentrations. Male and female mice had even greater incidences of alveolar/bronchiolar neoplasms of the lung, and many of the male mice in the highest exposure group died before the end of the study. Lesions including epithelial hyperplasia, inflammation, fibrosis, and squamous metaplasia occurred in the respiratory tract (nose, larynx, and lung) of male and female mice. Conclusions We conclude that exposure to vanadium pentoxide particles caused lung neoplasms in male rats and possibly in female rats, and in male and female mice.
Load more

Recommended publications
  • Oral Diagnosis: the Clinician's Guide
    Wright An imprint of Elsevier Science Limited Robert Stevenson House, 1-3 Baxter's Place, Leith Walk, Edinburgh EH I 3AF First published :WOO Reprinted 2002. 238 7X69. fax: (+ 1) 215 238 2239, e-mail: [email protected]. You may also complete your request on-line via the Elsevier Science homepage (http://www.elsevier.com). by selecting'Customer Support' and then 'Obtaining Permissions·. British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging in Publication Data A catalog record for this book is available from the Library of Congress ISBN 0 7236 1040 I _ your source for books. journals and multimedia in the health sciences www.elsevierhealth.com Composition by Scribe Design, Gillingham, Kent Printed and bound in China Contents Preface vii Acknowledgements ix 1 The challenge of diagnosis 1 2 The history 4 3 Examination 11 4 Diagnostic tests 33 5 Pain of dental origin 71 6 Pain of non-dental origin 99 7 Trauma 124 8 Infection 140 9 Cysts 160 10 Ulcers 185 11 White patches 210 12 Bumps, lumps and swellings 226 13 Oral changes in systemic disease 263 14 Oral consequences of medication 290 Index 299 Preface The foundation of any form of successful treatment is accurate diagnosis. Though scientifically based, dentistry is also an art. This is evident in the provision of operative dental care and also in the diagnosis of oral and dental diseases. While diagnostic skills will be developed and enhanced by experience, it is essential that every prospective dentist is taught how to develop a structured and comprehensive approach to oral diagnosis.
    [Show full text]
  • The Clinical Application of Della-Porta Et Al Score in a Mexican Patient with Myelodysplastic Syndrome
    CLINICAL CASE Rev Hematol Mex. 2020; 21 (3): 158-171. The clinical application of Della-Porta et al score in a Mexican patient with myelodysplastic syndrome. Aplicación clínica de la puntuación Della-Porta y colaboradores en un paciente mexicano con síndrome mielodisplásico Juan C Marín-Corte,1,4 Eduardo Olmedo-Gutiérrez,1,4 Jeny A Marín-Corte,5 Roberto N Miranda,3 Carlos E Bueso-Ramos,3 Omar Cano-Jiménez,1 Arturo R Fuentes-Reyes,1 Elizabeth Hernández-Salamanca,1,4 Miguel A López-Trujillo,1,4 Rafael A Marín-López,1,4 Guillermo J Ruiz-Delgado,1,2,4 Guillermo J Ruiz-Argüelles1,2,4 Abstract BACKGROUND: The myelodysplastic syndromes are one of the most studied diseases in hematology in recent years. By definition and according to the World Health Or- ganization Classification of Tumours of hematopoietic and Lymphoid Tissues 2017, myelodysplastic syndromes are a group of clonal hematopoietic stem cell diseases characterized by cytopenia, dysplasia in one or more of the major myeloid lineages, ineffective hematopoiesis, recurrent genetic abnormalities and increased risk of de- veloping acute myeloid leukemia (AML). To identify in a quick way this disease, we designed a worksheet based on the article of Matteo Della-Porta et al to developed a systematic approach to assess the morphological features in the bone marrow smears of three cell lineages in patients with myelodysplastic syndromes and provide the basis to validate flow cytometric and immunohistochemistry data. CLINICAL CASE: A 47-year-old male patient in whom we applied a worksheet that we designed based on Della-Porta score criteria to each cellularity lineage in the bone 1 Clinical Laboratories of Puebla; Puebla, marrow smears and we obtained significant results according to the bone marrow Puebla, México.
    [Show full text]
  • Tumour-Simulating Intrathoracic Marrow Heterotopia in Thalassaemia Major
    Thorax: first published as 10.1136/thx.19.2.121 on 1 March 1964. Downloaded from Thorax (1964), 19, 121 Tumour-simulating intrathoracic marrow heterotopia in thalassaemia major C. PAPAVASILIOU AND P. SFIKAKIS From the Department of Clinical Therapeutics, Alexandra Hospital, University of Athens Haemopoiesis under certain circumstances can be flat frontal bones, and a hard arched palate. The liver supplemented by extramedullary foci of hetero- was slightly enlarged. There was general enlargement topic bone marrow located in other tissues. In of the lymph nodes, particularly in the axillae. addition to the normal phenomenon of extra- Chronic ulcers were present in the region of the ankles. The haemoglobin was 8-7 g./ 100 ml., medullary haemopoiesis in newborn babies and haematocrit 27%, R.B.C. 3,520,000 with anisocytosis, infants, such a process has been observed, as a poikilocytosis, microcytosis, target cells, hypochromia, compensatory phenomenon, in conditions asso- and anisochromia. There were 7,150 white cells per ciated with abnormal function of haemopoietic c.mm. with 60% polymorphs, 36% lymphocytes, 3% tissue, such as pernicious anaemia, macrocytic eosinophils, and 1% monocytes. There were 9 anaemia of hepatic origin, osteosclerosis, exten- erythroblasts per 100 white cells in the peripheral sive neoplastic infiltration of the bones (leuk- blood. The serum bilirubin was 0-9 mg./100 ml. direct aemia, lymphoma, etc.), erythraemia, erythro- and 0-48 mg./ 100 ml. indirect. The bone marrow blastosis, acholuric jaundice, and thalassaemia. showed marked hyperplasia of the red cell series, the in white cell series, and of the megakaryocytes. There copyright. Heterotopic marrow has been described the was no anomaly in the maturation of the red cells.
    [Show full text]
  • Red Blood Disorders Anemia Med.Pdf 14.44MB
    Lviv National Medical University Department of pathological physiology PATHOLOGY OF RED BLOOD PhD. Sementsiv N.G. In norm The number of erythrocytes: in female - 3,9-4,7·1012/l in male - 4,5-5,0·1012/l Hemoglobin in female - 120-140g/l in male - 140-160g/l Color index(CI) - 0,85-1,15 Globular value = 3 x Hb / the first 3 figures of erythrocytes. Reticulocytes - 0.5-2%, 0,5-2%0 changes in total blood volume normovolemia hypovolemia hypervolemia simple (Ht - norm), polycitemia (Ht > 0,48), olygocytemia (Ht < 0,36). A) Norm B) acut anaemia б) acute hemorrhage г) hydremia Pathological forms of erythrocytes regenerative degenerative cell pathologic regeneration Regenerative forms reticulocytes залежно від зрілості розрізняють: (Зернисті) Stippling (Сітчасті) Mesh Norm in a blood reticulocytes - 0,2–2,0%. Regenerative forms Basophiles substantial erythrocytes - cytoplasm remains basophilic normo blast. Polychromatophil erythrocytes (polychromasia, polychromatophilia ) – erythrocytes with basophiles substantial ( blue cells) indicates increased RBC production by the marrow Qualitative (degenerative) changes of red blood cell - poikilocytosis - different shape of erythrocytes; - anisocytosis - different size of erythrocytes; - anisochromia - different saturation of red blood cells by hemoglobin Degenerative forms Anisocytosis present in a blood different forms erythrocytes » normocyte (7,01–8,0 мкм) » microcyte(6,9–5,7 мкм) » macrocyte(8,1–9,35 мкм) » megalocyte (10–15 мкм) Degenerative forms Poikilocytosis present in a blood pictures erythrocytes different forms : elongate form , oval, ellipsoid and os. ОVAlOCYTE( ELLIPTOCYTE) – 5% all blood. Pathological cells regenerate Megaloblast mehaloblastyc cell type hematopoiesis Megaloblast oval cells in the diameter of 1,5- 2,0 times larger than normal erythrocytes is the final stage mehaloblastyc hematopoiesis.
    [Show full text]
  • Erythroleukemia with Complex Cytogenetic Abnormalities: a Case Report with Review of Literature
    RESEARCH PAPER Medical Science Volume : 3 | Issue : 7 | July 2013 | ISSN - 2249-555X Erythroleukemia with Complex Cytogenetic Abnormalities: A case report with review of literature KEYWORDS Acute Erythroleukemia, Flow cytometry, Cytogenetic abnormality Pooja K Suresh Purnima S Rao Urmila N Khadilkar Department of Pathology, Kasturba Department of Pathology, Kasturba Department of Pathology, Kasturba Medical College, Mangalore (Manipal Medical College, Mangalore (Manipal Medical College, Mangalore (Manipal University) University) University) ABSTRACT Acute Erythroleukemia (AEL) is a rare type of hematopoietic neoplasm, having a prevalence of 3-5% of all Acute Myeloid Leukemia (AML). We present a case report of acute erythroleukemia, a rare type of AML, with complex cytogenetic abnormalities. A 54-year old male presented with low grade fever and significant weight loss. Complete hemogram and a peripheral smear revealed pancytopenia with 18% blasts. It also showed features of hemolysis. Bone marrow (BM) study showed eryth- roid hyperplasia with erythroblasts constituting 85% of all nucleated cells and 21% myeloid blasts among non-erythroid cells. Flow cytometry revealed 23% blasts positive for CD33, CD34, CD117, CD36 and HLA-DR. Cytogenetic study revealed hypotetraploidy with numerous structural abnormalities indicating poor prognosis. Introduction cells. Of this, the proerythroblasts comprised 35%. Dyspoi- The term Acute Erythroleukemia (AEL) /AML-M6 is defined etic erythroid cells showing multinucleation, nuclear budding as proliferation of dysplastic erythroid elements mixed with and nuclear to cytoplasmic dysynchrony were noted. Myelo- blasts of myeloid origin. The recent World Health Organi- blasts comprised 21% of non erythroid cells. Megakaryocytes zation (WHO) classification has a category of acute myeloid were normal in number and morphology.
    [Show full text]
  • Acute Erythroid Leukemia: a Review
    110 Apr 2012 Vol 5 No.2 North American Journal of Medicine and Science Review Acute Erythroid Leukemia: A Review Daniela Mihova, MD, FCAP;1* Lanjing Zhang, MD, MS, FCAP2,3 1 Pathology Department and Clinical Laboratories, Flushing Hospital Medical Center, Flushing, NY 2 Department of Pathology, University Medical Center at Princeton, Princeton, NJ 3 Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School-UMDNJ, New Brunswick, NJ Acute erythroid leukemia is a rare form of acute myeloid leukemia. It accounts for <5% of all acute myeloid leukemia cases. According to the World Health Organization 2008 classification, it falls under the category of acute myeloid leukemia, not otherwise specified and is further divided into two subtypes: erythroid leukemia (erythroid/myeloid) and pure erythroid leukemia. Currently, erythroleukemia (erythroid/myeloid) is defined as 50% or more erythroid precursors and ≥20% blasts of the non-erythroid cells. By definition, pure erythroid leukemia is composed of ≥80% erythroid precursors. Acute erythroid leukemia is a diagnosis of exclusion and difficulty. This review discusses its differential diagnoses, which present with erythroid proliferation, such as myelodysplastic syndrome with erythroid proliferation, acute myeloid leukemia with myelodysplasia related changes, therapy related acute myeloid leukemia, myeloproliferative neoplasms with erythroblast transformation, acute myeloid leukemia with recurrent genetic abnormalities and other types of hematologic neoplasms. Additionally, reactive conditions such as erythropoietin treatment, vitamin B12 and folate deficiency, toxin exposure and congenital dyserythropoiesis should be excluded. As a result, the frequency of acute erythroid leukemia diagnosis has been reduced. Important adverse prognostic factors will be summarized, including presence of complex cytogenetic karyotype as the most important one.
    [Show full text]
  • Щетинин Патофизиол Ч2 Англ 9-10-19.Indd
    The Federal State Budgetary Educational Institution of Higher Education «Stavropol State Medical University» The Ministry of Healthcare of the Russian Federation The Department of Pathological Physiology PATHOPHYSIOLOGY, CLINICAL PATHOPHYSIOLOGY (WITH THE BASICS OF THE ORGANIZATION OF STUDENTS’ INDEPENDENT WORK) Specialty 31.05.01 General Medicine Part II STUDY GUIDE FOR FOREIGN STUDENTS OF THE ENGLISH-SPEAKING MEDIUM OF MEDICAL UNIVERSITIES Stavropol, 2019 1 УДК 616-092 (072) ББК 52.52я73 Р30 Pathophysiology, clinical pathophysiology (with the basics of the organization of students’ independent work), Part II: Study Guide / E.V. Schetinin, M.Yu. Vafiadi, G.G. Petrosyan, N.G. Radzievskaya, L.D. Erkenova, L.A. Parazyan, Yu.Yu. Gatilo, A.A. Vafiadi – Stavropol: Publishing house: StSMU, 2019. – 336 p. Authors: Professor E.V. Schetinin, Assoc. Professor M.Yu. Vafiadi, Assoc. Professor G.G. Petrosyan, ass. N.G. Radzievskaya, ass. L.D. Erkenova, ass. L.A. Parazyan, ass. Yu.Yu. Gatilo, ass. A.A. Vafiadi. ISBN 978-5-89822-595-7 Ч. I – 336 с. ISBN 978-5-89822-632-9 The study guide was developed in accordance with the Federal State Educational Standard of Higher Education and modern programs in Pathophysiology, Clinical Pathophysiology in the specialty 31.05.01 General Medicine. The study guide is designed for foreign students of the English-speaking Medium of medical universities to carry out practical work during class hours and homework assignments for each studied topic in Pathophysiology, Clinical Pathophysiology with the basics of organizing
    [Show full text]
  • Clinical Hematology 1
    CLINICAL HEMATOLOGY 1 CLINICAL HEMATOLOGY Editor Gamal Abdul Hamid, MD,PhD Associate Professor Faculty of Medicine and Health Sciences University of Aden CLINICAL HEMATOLOGY 2 PREFACE Clinical Hematology, first edition is written specifically for medical students, the clinician and resident doctors in training and general practioner. It is a practical guide to the diagnosis and treatment of the most common disorders of red blood cells, white blood cells, hemostasis and blood transfusion medicine. Each disease state is discussed in terms of the pathophysiology, clinical and paraclinical features which support the diagnosis and differential diagnosis. We bring together facts, concepts, and protocols important for the practice of hematology. In addition this book is also supported with review questions and quizzes. G.A-H 2012 CLINICAL HEMATOLOGY 3 CONTENTS Preface 1. Hematopoiesis 7 2. Anemia 26 3. Iron Deficiency Anemia 32 4. Hemolytic Anemia 41 5. Sickle Cell Hemoglobinopathies 49 6. Thalassemia 57 7. Hereditary Hemolytic Anemia 63 8. Acquired Hemolytic Anemia 68 9. Macrocytic Anemia 75 10. Bone Marrow Failure, Panctopenia 87 11. Spleen 95 12. Acute Leukemia 99 13. Chronic Myeloproliferative Disorders 125 14. Chronic Lymphoproliferative Disorders 137 15. Malignant Lymphoma 147 16. Multiple Myeloma and Related Paraproteinemia 171 17. Hemorrhagic Diseases 179 18. Transfusion Medicine 201 19. Bone Marrow Transplantations 214 CLINICAL HEMATOLOGY 4 Appendices: I. Hematological Tests and Normal Values 221 II. CD Nomenclature for Leukocytes Antigen 226 III. Cytotoxic Drugs 228 IV. Drugs Used in Hematology 230 Glossary 232 Answers 246 Bibliography 247 CLINICAL HEMATOLOGY 5 CLINICAL HEMATOLOGY 6 HEMATOPOIESIS 1 All of the cells in the peripheral blood have finite life spans and thus must be renewed continuously.
    [Show full text]
  • Induction of Hyperchromic Microcytic Anaemia by Repeated Oral
    The Journal of Toxicological Sciences (J. Toxicol. Sci.) 957 Vol.37, No.5, 957-968, 2012 Original Article Induction of hyperchromic microcytic anaemia by repeated oral administration of methotrexate in rats Sayuri Kojima, Toshinori Yoshida, Junya Sasaki, Naofumi Takahashi, Maki Kuwahara, Yasufumi Shutoh, Machiko Saka, Nobuaki Nakashima, Tadashi Kosaka and Takanori Harada The Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso-shi, Ibaraki 303-0043, Japan (Received June 20, 2012; Accepted July 21, 2012) ABSTRACT — Anaemia is a significant prognostic factor in cancer patients receiving anticancer drugs such as methotrexate (MTX). This study focuses on the effects of toxicological changes on the hemat- opoietic systems in male and female Wistar Hannover rats when MTX is orally administered at a dose of 0, 0.05, 0.15, or 0.45 mg/(kg·day) for a period of 28 days. Both male and female rats receiving 0.45 mg/kg MTX showed a decrease in the haemoglobin concentration (Hb), haematocrit, and erythrocyte count. Female rats showed a decrease in mean corpuscular volume (MCV) and an increase in cell mean Hb (CHCM) in total erythrocytes, including the mature erythrocytes. These results indicate that MTX caus- es the production of small, mature erythrocytes that contain a high concentration of Hb. MTX reduced the number of peripheral reticulocytes but produced the cells with a large size and a high concentration of Hb, as demonstrated by the reticulocyte MCV and CHCM as well as the content of haemoglobin per reticulocyte (CHr). Consistent with these findings, bone marrow haematopoiesis was impaired by MTX, as there was a reduction in erythroid count in rats of both sexes.
    [Show full text]
  • Pheripheral Smear Examination
    Indication of peripheral blood smear exmination: 1. For carried out differential WBC count. 2. For differential diagnosis of anemia. 3. For detection of parasites. 4. For diagnosis of leucemoid reaction. 5. For diagnosis and differential diagnosis of leukemia. 6. For detection of platelet abnormalities. 7. For diagnosis of conditions like infectious mononucleosis. 1) RBC series 2) WBC series 3) Platelets 4) Parasites 5) Other abnormal cells final diagnosis with advice 1. Abnormalities of Haemoglobin content:- Hypochromia Hyperchromia Anisochromia Polychromatophilia 2. Abnormalities of size of red cells:- Microcytosis Macrocytosis Anisocytosis 3. Abnormalities of shape of red cells ( Poikilocytosis ):- different abnormal shapes of RBC I. Elliptocytosis II. Spherocytosis III. Target cells IV. Schistocytosis V. Acanthocytois VI. Crenated cells VII. Sickled cells VIII. Leptocytes 4. Abnormalities of structure of red cells:- •Basophilic stippling ( Punctate basophilia ) •Howell- jolly bodies •Cabot rings •Pappenheimer bodies •Malarial stippling •Rouleaux formation •Agglutination •Nucleated red cells •No nucleus, enzyme packets •Biconcave discs – Haem + Gl •Center 1/3 pallor •Pink cytoplasm (Hb filled) •Cell size 7- 8 µ - capill. 2 µ •EM pathway, HMP •Negative charge – no phago •Na less, K more inside •100-120 days life span Hypochromic Microcytic The RBC‘s here are smaller than normal and have an increased zone of central pallor. This is indicative of a hypochromic (less hemoglobin in each RBC) microcytic (smaller size of each RBC) anemia. There is also increased anisocytosis. Microcytic the average size of erythrocytes is smaller than normal Macrocytic Note the hypersegmented neurotrophil and also that the RBC are almost as large as the lymphocyte. Finally, note that there are fewer RBCs.
    [Show full text]
  • Morphologic Evaluation of Anemia – I Adewoyin S
    nd M y a ed g ic lo i o n i e B Adewoyin and Ogbenna, Biol Med (Aligarh) 2016, 8:6 DOI: 10.4172/0974-8369.1000322 ISSN: 0974-8369 Biology and Medicine Review Article Open Access Morphologic Evaluation of Anemia – I Adewoyin S. Ademola1* and Ogbenna A. Abiola2 1Department of Haematology and Blood Transfusion, University of Benin Teaching Hospital, PMB 1111, Ugbowo, Benin City, Nigeria 2Department of Haematology and Blood Transfusion, Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria *Corresponding author: Adewoyin S. Ademola, Department of Haematology and Blood Transfusion, University of Benin Teaching Hospital, PMB 1111, Ugbowo, Benin City, Nigeria, Tel: +2347033966347; E-mail: [email protected] Received date: June 20, 2016; Accepted date: July 15, 2016; Published date: July 22, 2016 Copyright: © 2016 Adewoyin AS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. Abstract Anaemia is a feature of many tropical diseases. Anaemia diagnosis therefore remains a crucial intervention among physicians in developing countries. A barrage of laboratory test (anaemic work-up) is usually deployed in differentiating its underlying cause. However, central to anaemia evaluation is the morphology of the red cells and other cell lines. Conventionally, initial laboratory tests include full blood count, reticulocyte count and peripheral blood film (PBF). PBF is often a clinical request, performed by skilled technologist and reported by haematologist/ haematomorphologist. Findings from PBF are reviewed and reported in the light of patient’s clinical history and examination findings.
    [Show full text]
  • Red Blood Disorders Anemia
    Lviv National Medical University Department of pathological physiology PATHOLOGY OF RED BLOOD PhD. Sementsiv N.G. In norm The number of erythrocytes: in female - 3,9-4,7·1012/l in male - 4,5-5,0·1012/l Hemoglobin in female - 120-140g/l in male - 140-160g/l Color index(CI) - 0,85-1,15 Globular value = 3 x Hb / the first 3 figures of erythrocytes. Reticulocytes - 0.5-2%, 0,5-2%0 changes in total blood volume normovolemia hypovolemia hypervolemia simple (Ht - norm), polycitemia (Ht > 0,48), olygocytemia (Ht < 0,36). A) Norm B) acut anaemia б) acute hemorrhage г) hydremia Pathological forms of erythrocytes regenerative degenerative cell pathologic regeneration Regenerative forms reticulocytes залежно від зрілості розрізняють: (Зернисті) Stippling (Сітчасті) Mesh Norm in a blood reticulocytes - 0,2–2,0%. Regenerative forms Basophiles substantial erythrocytes - cytoplasm remains basophilic normo blast. Polychromatophil erythrocytes (polychromasia, polychromatophilia ) – erythrocytes with basophiles substantial ( blue cells) indicates increased RBC production by the marrow Qualitative (degenerative) changes of red blood cell - poikilocytosis - different shape of erythrocytes; - anisocytosis - different size of erythrocytes; - anisochromia - different saturation of red blood cells by hemoglobin Degenerative forms Anisocytosis present in a blood different forms erythrocytes » normocyte (7,01–8,0 мкм) » microcyte(6,9–5,7 мкм) » macrocyte(8,1–9,35 мкм) » megalocyte (10–15 мкм) Degenerative forms Poikilocytosis present in a blood pictures erythrocytes different forms : elongate form , oval, ellipsoid and os. ОVAlOCYTE( ELLIPTOCYTE) – 5% all blood. Pathological cells regenerate Megaloblast mehaloblastyc cell type hematopoiesis Megaloblast oval cells in the diameter of 1,5- 2,0 times larger than normal erythrocytes is the final stage mehaloblastyc hematopoiesis.
    [Show full text]