Atlas of Hematology
by John Meletis
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PREFACE OF THE AUTHOR
Many years after the first publication of the CD-ROM “Atlas of Hematology”, CD-ROM “Hematology-Diagnostic approach”, sixth edition of the book “From the Hematological finding to diagnosis" and the Greek edition of the book "Atlas of Hematology" the encouraging comments by senior and younger Colleagues of diverse specialties, and also by Students, promoted encouraged me to improve my contribution. Therefore, I am publishing the English version of the “Atlas of Hematology” with almost 4000 colored pictures of microscopic preparations, with a special emphasis in diagnostic and educational aspects.
“A picture counts for more than thousand words” we use to say in Greece. This is particularly the case in hematology, as the familiarization and the long-lasting observation of hematological preparations is the base for a correct diagnostic approach. The observation of preparations is essential for hematology education. Each patient has “his own disease” and cellular morphology often varies considerably, depending on the case.
Really every preparation is accompanied by a brief text describing the basic objects of the picture. The Atlas also includes several pictures of the same subject or disorder. Similarities in morphology give the reader the theoretical and practical access in the variability of hematological cytology.
I know that several editions on Hematology illustrated already exist in the literature. In my opinion the present work gives the reader the possibility to observe many preparations of the same object; something which not provided by other Authors due to limited space and cost. The legends that accompany the pictures present the basic components of the nature of the cells and the morphologic criteria for their recognition. Pictures are sometimes of low quality, in contrast to the majority of books that include ideal pictures, after a certain “retouche”. I have included these pictures as hematologists do not often observe “perfect” preparations in their daily routine practice. Thus, I believe that morphologist has to be familiarized with pictures of preparations with no sufficient coating, rapid staining, low quality of staining, monochromatic staining, change of usual nuances due to the absence of “standard” pH, cleaned coatings after immersion in xylose, remaining of the coating for a long time in oil, villain rinsing after the pigmentation and many other accidental events, often unavoidable, however hematologist is called to observe, diagnose, and take rapid decision through such preparations. Moreover, as advised by my Mentors, the observation of slides like these is obligatory for those who practice in “fighting” hematology.
A well known feature is that hematological diagnosis in the past was mainly based on observation, which is considered to be “the best school” for someone to reach shortly and accurately at a correct diagnosis. Therefore, I wanted to share my experience through this Atlas with younger hematologists and to offer the more general and established practice.
It is time that nowadays in Medicine particularly in hematological diagnostic procedure things tend to be turned into a computerized process. The facility of performance of several, even sometimes complicated, laboratory tests and measurements, and the magic of automatic analyzers and computers have a tendency to override more established and accurate “old” methods. However, the "magic" of diagnostic approach using information from the patient’s history, clinical examination, evaluation of simple hematological and biochemical measurements and particularly observation of blood and bone marrow slides, is very attractive and impressively interesting. It remains also necessary to achieve objective and correct diagnosis.
Likewise, this procedure contributes to the way of medical thinking, and the logical approach to correct diagnosis through a step by step process, by using the evaluation of simple hematological parameters and observations. My effort has the final aim to help the new Colleagues, who try to move from theory to the practical approach of the hematological patient. New Colleagues who found themselves alone and frequent self conscious when they confront for the first time the patient followed by a variety and sometimes useless examinations. Moreover, this approach cannot substitute the very important, books of Hematology, but it can be a useful tool for the rapid approach of clinical hematological problems, in daily practice. Thus, the thorough analysis of a hematological disorder has been replaced by brief proposals, tables, diagnostic tools, evaluation of clinical and laboratory data, aiming to the suitable diagnosis, which is given concisely almost telegraphically; thus leaving the reader an approach of the subject in extensive specialized books and articles. I believe that this Atlas will constitute a useful tool for new Doctors, and Students of Medicine and everyone who deals with blood cytology.
Our work would be impossible to be released without the laborious and long-lasting effort for the electronic transport and regularization of pictures by my son Christos Meletis, Electrician Engineer and Engineer of Computers. Our interminal hours of collaboration and hard work for the composition and completion of this Atlas, gave us a good example of labor, effort, difficulties, charming, pleasure, satisfaction and finally conquest that filled with joy an Academic Teacher, but also a new Scientist who tried to give his knowledge from the "birth of" similar essay. This cheerful combination proves the necessity for a collaboration between “old” generation of hematologists/morphologists with the “new” generation of scientists of electronic and digital techniques for the benefit of hematology and the transport of knowledge.
Very much encouragement and assistance in my effort was given by my beloved Colleagues and Friends, Nora Viniou, Kostas Konstantopoulos, John Rombos, Vangelis Terpos, John Kakkas, Stathis Papavassiliou, Marina Mantzourani, Filippos Deligiannis, Stathis Vavourakis, Christos Poziopoulos, Michalis Samarkos, Helen Chandrinou, Lia Tsimberidou, Effie Apostolidou, Veroniki Komninaka, Maria Tsironi, Kostas Korovesis, Stergios Tassiopoulos, Kostas Anargyrou, Pericles Melas, Olga Mpenopoulou, Elsa Kampos, Eutyxia Mitilineou, Theodoros Vassilakopoulos, Angelos Sarantopoulos, Antonis Antoniadis, Cleio Chatziara, Thanasis Karagiannis, Telemachos Antoniou, Theocharis Sinifakoulis, Aleka Petrou, Charis Floudas, Nikos Euaggelatos, Xanthoula Giakoumi and Matina Chatzinikolaou who helped in the improvement and completeness of this publication, through their valuable comments. They represented the "other side", the people this Atlas was written for, and I would like to thank them kindheartedly. I would also like to thank my dear Colleagues Xenophon Yataganas, Heleni Variami, Elpi Kritikou-Griva and Aphrodite Loutradis-Anagnostou who gave me preparations from their personal archive.
Every time I also thank and express my appreciation in my Professors Phaedon Fessas, Dimitris Loukopoulos, George Eliopoulos and Xenophon Yataganas, who initiated me into the magnificent world of blood cytology as well as in my Professors and Friend Fotis Pavlatos, Phaedon Kaklamanis, Elias Fokas, George Stamatellos, Thomas Tassiopoulos and Anastasia Tassiopoulou in whom I owe my hematological and medical education in the First Department of Internal Medicine, University of Athens School of Medicine. It is certain that without their own presence in my medical career, it would not be possible the creation of this work.
Year-round I would particularly like to thank and to express my immense love in Mrs Maria Tsogas for the endless hours of collaboration needed for her fantastic work, help, support and moral reinforcement during the preparation of this Atlas. Without her precious help this effort would never have been completed.
Overall, I would like to express my thanks to the painter Mrs Lilly Eleftheriou who made me the great honor to paint the cover of this Atlas, thus giving to all of us the occasion to move through our thought and imagination from everyday routine to the attractive space of artistic enjoyment. Finally I want to express all my respects and thanks to my Maitre Mr. Lucien Brown for his painstaking grammatical and linguistic corrections that would be impossible without his own precious help.
Ultimately I particularly thank all the personnel of Publications "Nireas", especially my good friend Vasilis Katoufas for his encouragement for the releasing this publication and my dear daughter Rallou Meleti for her essential and precious help with inexhaustible ideas for artistic care in configuring the atlas, devoting to it interminable effort and time.
John Meletis MD, PhD
Professor in Medicine and Hematology
Athens 2010
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Atlas of Hematology
March 2009, Nereus editions
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CONTENTS
CHAPTER 1
AN APPROACH TO DIAGNOSIS BASED ON PERIPHERAL BLOOD SMEAR OBSERVATION
Peripheral blood smear……………..5
Sources of error………………………………………5
Fixation……………………………………..6
Stain types……………………………………..6
Sources of error……………………………………..6
Smear examination.....………………….6
Red cell morphology……………………………..7
Fluctuation in shape and hemoglobinization…………8
Fluctuation in size (anisocytosis)……………………………..9
Disorders of stain quality……………………..9
Red cell inclusions………………………..9
CHAPTER 2
ERYTHROID SERIES
Hemopoietic cell characteristics…………15
Pluripotent stem cell...........................15
Myeloid stem cell...........................15
CFU-GEMM........................15
Identifiable cells of erythroid series.................15
Erythroblastic island.......................15
Proerythroblast………………………………….15
Basophilic erythroblast………………………..15
Polychromatophilic erythroblast……………….16
Acidophilic or orthochromatic erythroblast……………………………16
Reticulocyte………………………………...16
Erythrocyte…………………………………..16
CHAPTER 3 GRANULOCYTIC SERIES
Hemopoietic cell characteristics…………23
Pluripotent stem cell...........................23
Myeloid stem cell...........................23
Identifiable cells of erythroid series.................23
Myeloblast………………………………………….23
Promyelocyte…………………………………….23
Myelocyte………………………………………….23
Metamyelocyte……………………………………23
Band cell……………………………………….24
Neutrophil…………………………………24
Eosinophil………………………………………24
Basophil…………………………………………24
Mast cell…………………………………….24
CHAPTER 4 MONOCYTIC SERIES
Hemopoietic cell characteristics…………….35
Identifiable cells of monocytic series………35
Monoblast…………………………………………….35
Promonocyte…………………………………………35
Monocyte……………………………………………..35
CHAPTER 5 LYMPHOID SERIES
Lymphoid stem cell…………….47
Identifiable cells of the lymphoid series…………..47
B lymphoblast…………………………………………47
Pre-B lymphocyte…………………………………...47
B lymphocyte…………………………………………47
Plasmacyte…………………………………47
T-lymphoblast…………………………………..47
Pre-T lymphocyte……………………………..47
T lymphocyte…………………………………47
CHAPTER 6 MEGAKARYOCYTIC SERIES
Hemopoietic cells characteristics…………………….55
Identifiable cells of megakaryocytic series……….55
Megakaryoblast……………………..55
Megakaryocyte……………………………………………..55
Platelet……………………………………………………...55
CHAPTER 7 RED CELL MORPHOLOGY ALTERATIONS IN THE PERIPHERAL BLOOD SMEAR
Bad blood smear………………………………61
Acanthocytosis……………………………61
Anisocytosis………………………………61
Anisochromy…………………………………61
Dacryocytes……………………………61
Double red cell population……………………………61
Drepanocytosis…………………………61
Elliptocytosis…………………………61
Echinocytes…………………………….62
Keratocytes………………………………62
Knizocytes…………………………………62
Helmet cells (cranocytes)………………………………..62
Codocytes……………………………..62
Leptocytosis…………………………….62
Macrocytosis……………………………62
Macrocytosis with oval red cell shape (megalocytosis)...62
Microcytosis…………………………….62
Poikilocytosis………………………….62
Polychromatophilia………………………….62
Pycnocytes………………………………63
Rouleaux formation…………………………………….63
Stomatocytosis………………………..63
Target cells…………………………..63
Spherocytosis………………………….63
Schistocytosis…………………………..63
"Bite" erythrocytes………………………..63
Hyperchromy…………………………………63
Hypochromy…………………………………..63
CHAPTER 8 ERYTHROCYTIC INCLUSION BODIES
Basophilic stippling………………….93
Cabot ring…………………..93
Nucleated erythrocytes……………….93
Siderocytes (Pappenheimer bodies)…………………..93
Heinz bodies…………………….93
Howell-Jolly bodies……………..93
Reticulocytosis…………93
CHAPTER 9 OTHER BONE MARROW CELLS
Macrophage…………………103
Mast cell………………103
Osteoblast……………….103
Osteoclast……………….103
Tissue neutrophil…………103
Tissue eosinophil…………….103
Lipocyte……………………103
CHAPTER 10 LEUCOCYTE ABNORMALITIES IN PERIPHERAL BLOOD SMEAR
Chediak-Higashi anomaly……………………….111
May-Hegglin anomaly…………………………….111
Pelger-Huet anomaly………………………………111
Döhle bodies……………………………………….111
Toxic granulation…………………………………….111
Auer rods or bodies……………………………..111
Leukocytosis……………………………………..111
"Shift to the left" of the granulocytic series…………………………….111
Myelemia.............................................111
"Shift to the right" of the granulocytic series………………………………..111
Leukoerythroblastic reaction…………………..112
Atypical lymphocytes…………………………………112
Smudge cells……………………………………….112
Lymphocytosis……………………………………..112
CHAPTER 11 BONE MARROW SMEARS EVALUATION
Evaluation of bone marrow smears........................127
Normal bone marrow - cellularity………...129
Hypercellular bone marrow………………………….129
Hypocellular bone marrow (aplastic)……………………………129
Granulocytic/erythroid series ratio (G/E)……..129
Erythroid series hyperplasia…………………129
Erythroid series hypoplasia…………………129
Retardation of hemoglobinization…………….129
Granulocytic series hyperplasia……………..129
Granulocytic series hypoplasia………………129
Megakaryocytic series hyperplasia……….129
Megakaryocytic series hypoplasia…………129
Perturbation of the erythroid series cells…………………………..129
Vacuolated erythroblasts…………………..129
Retardation of hemoglobinization……………129
Megaloblastosis……………………………….129
Dyserythropoiesis………………………………130
Perturbation of the granulocytic series………………..130
Giant cells…………………………………130
Maturation arrest……………………………130
Lymphocytosis or monocytosis…………….130
Leukemic cells………………………………..130
Stroma cell hyperplasia…………………..130
Erythrophagocytosis-hemophagocytosis……………..130
Macrophages containing lipoid particles…………………………………130
Lymphoplasmacytoid cells…………..130
Plasmacytosis……………………………..130
Reed-Sternberg cells…………………………131
Lymphomatic infiltration…………………….131
Malignant cells………………….131
Bone marrow necrosis………………………….131
Ferrum…………………………………….131
Ring sideroblasts……………..131
CHAPTER 12 ERYTHROID SERIES DISORDERS
Hypochromic microcytic anemia……………….163
Iron deficiency anemia……………………………163
Sideroblastic anemia………………………..164
Normochromic macrocytic anemia………….168
Megaloblastic anemia……………………….169
Normochromic normocytic anemia…………180
Erythroblastopenia………………………….181
Aplastic anemia………………………182
Hereditary spherocytosis…………183
Hereditary elliptocytosis…………..184
Hereditary pyropoikilocytosis……….184
Thalassemia syndromes………………………190
β-thalassemia………………….190
α-thalassemia……………………192
Hemoglobin S disease (sickle cell anemia)……………….193
Hemoglobin C disease…………………..194
G6PD deficiency……………………….205
Pyruvate kinase deficiency………………206
Rare enzymopathies...........................206
Autoimmune hemolytic anemia……………………211
Hemolytic anemias with negative Coombs test……………..213
Hemolytic anemias due to mechanical reasons…………………..213
Hereditary dyserythropoietic anemias………………224
CHAPTER 13 GRANULOCYTIC AND MONOCYTIC SERIES DISORDERS
Source-physiology of granulocytes and monocytes………….231
Disorders of granulocytes-monocytes…………………………..232
Neutrophilia…………………………………..232
Neutropenia…………………………233
Agranulocytosis…………………….236
Eosinophilia…………………………….236
Hypereosinophilic syndrome…………236
Basophilia………………………………237
Mastocytosis………………………237
Monocytosis…………………………237
Monocytopenia……………………..237
Alterations of monocytes/macrophages....................237
CHAPTER 14 LYMPHOID SERIES DISTURBANCES
Alterations of absolute lymphocyte number..................245
Lymphocytosis………………………….245
Lymphopenia………………………………..245
Qualitative alterations of the lymphoid series cells…………..246
Infectious mononucleosis…………………………..247
CHAPTER 15 MYELODYSPLASTIC SYNDROMES
Findings characteristic of dyserythropoiesis……………257
Findings characteristic of dysgranulopoiesis……………..257
Findings characteristic of dysmagakaryopoiesis………..258
Refractory anemias-myelodysplastic syndromes…………258
Refractory anemia…………………………………………………258
Refractory anemia with ring sideroblasts………….258
Refractory anemia with excess of blasts………………………259
Refractory anemia with excess of blasts in transformation………259
Chronic myelomonocytic leukemia……………………………259
5q- syndrome……………………………………………………259
CHAPTER 16 MYELOPROLIFERATIVE DISORDERS
Chronic myelogenous leukemia……………………………..291
Myelofibrosis……………………………………………302
Polycythemia…………………………………………………311
Essential polycythemia………………………………312
Essential thrombocythemia……………………………314
Thrombocytosis………………………………………..314
Hypersplenism…………………………………………..315
CHAPTER 17 LEUKEMIAS
Patient approach in cases with circulating blastic cells…………319
Blast cell morphology……………………………………………………….319
Distinction of blasts from other "blast-like" cells……………………….319
Morphological "identification" of blast cells…………………………………..319
Estimations of the other parameters of hematology analysis…………………319
Disorders related with the presence of blasts in the peripheral blood…….320
Cytochemical staining for acute leukemia classification………….320
Antibodies useful in diagnosis and classification of leukemia…………….321
Classification of acute non lymphoblastic leukemia………………………………….322
Acute undifferentiated leukemia, Μ0 FAB …………………………………………322
Acute myeloblastic leukemia without maturation, Μ1 FAB …………..325
Acute myeloblastic anemia with maturation, Μ2 FAB ……………….326
Acute promyelocytic leukemia, Μ3 FAB ………………………….
Acute myelomonocytic leukemia, Μ4 FAB …………………………
Acute monoblastic leukemia, Μ5a FAB ……………………………..
Acute monocytic leukemia with differentiation, M5b FAB ……………………………..
Erythroleukemia, Μ6 FAB ………………………………………..
Acute megakaryoblastic leukemia, Μ7 FAB …………………………
Mixed leukemias…………………………………………………………..
Acute basophilic leukemia……………………………………………….
Mast cell leukemia……………………………………………
Acute eosinophilic leukemia………………………………………………
Acute lymphoblastic leukemia…………………………………………..
Morphologic, cytochemical and cytogenetic features of ALL………..
Immunophenotype of ALL………………………………..
Classification of ALL……………………………………….
Acute lymphoblastic leukemia, L1 FAB………
Acute lymphoblastic leukemia, L2 FAB ………………….
Acute lymphoblastic leukemia, L3 FAB ………………….
CHAPTER 18 MALIGNANT AND BENIGN LYMPHOPROLIFERATIVE SYNDROMES
Chronic lymphoid leukemia………………………..
Chronic T-cell lymphocytosis…..
T-chronic lymphoid leukemia………………………….
Large granular cell lymphocytosis (T-cell LGL)……….
NK-cell LGL………434
T-chronic prolymphocytic leukemia……………
B-chronic prolymphocytic leukemia……………
Leukemic phase of anon-Hodgkin lymphoma…………
Splenic lymphoma with villous lymphocytes…………
Sézary's syndrome………………………………………
Adult T-leukemia/lymphoma……………………….
Hairy cell leukemia……………………..
Hodgkin's disease……………………………………
Angioimmunoblastic lymphadenopathy……………
Non-Hodgkin's lymphomas……………………………….
Mantle cell lymphoma…………………..
MALT lymphomas……………………………………….
B-cell thymic lymphoma……………………..
CHAPTER 19 MULTIPLE MYELOMA
Multiple myeloma………………………………..
Plasmacytic leukemia………………………..
CHAPTER 20 PLATELET AND COAGULATION DISORDERS
Hemogramme information on platelets……………
Source of blood…………………………………………………
Normal characteristics of platelets………………………...
Platelet counting………………………………………………….
Normal platelet values-normal variations………………………………………
Informations from the peripheral blood smear……………….
Variations of platelet numbers…………………………..
Causes of an artificial thrombocytopenia…………………………………………..
Morphology - staining……………………………………………..
“Platelet parameters”………………………………………….
Immune thrombocytopenic purpura……………………………………
Giant platelets, Bernard-Soulier syndrome………………….
Disseminated intravascular coagulation……………………………………………..
CHAPTER 21 MICROORGANISMS
Malaria…………………………………..
Trypanosomiasis………………………..
Visceral leishmaniasis………………………………
Toxoplasmosis…………………………..
Babesiosis……………………………
Filariasis…………………………………
Fungal infections……………………………….
Bartonellosis………………………….
Relapsing fever……………………
CHAPTER 22 HISTOCHEMICAL STAINING
Myeloperoxidase……………………………..
Sudan Black B…………………………….
Leucocyte alkaline phosphatase…………..
PAS…………………………………………
Acid phosphatase…………………………
Napthol AS-D cloroacetate esterase……
Napthol ASD acetate esterase…………..
α-Napthyl acetate esterase………………
Double esterase reaction…………….
Ferrum (Prussian blue)……..……………
Ringed sideroblasts……………
Kleihauer-Betke reaction………………
F-cells………………………………….
Inclusion bodies………………………………….
CHAPTER 23 ΑRTIFACTS
Artifacts……………………………………….
False echinocytosis……………………
Rapid fixation………………………..
Precipitation of staining…………………………
Crescent formations……………………..
Apoptotic cells……………………….
CHAPTER 24 MALIGNANT CELLS - HISTIOCYTOSIS
Neoplasmatic metastases…………………..
Lipoidoses…………………………………….
Macrophage containing lipoids………………………..
Histiocytosis…………………………….….
Langerhans cell histiocytosis…….
Malignant non-Langerhans cell histiocytosis………
Malignant histiocytosis…………………………………………
Reactive hemophagocytic syndrome………………………
Sinus histiocytosis with massive lymphadenopathy……………
Hemophagocytic syndrome accompanied by viral infections…………………..
CHAPTER 25 BIOLOGICAL FLUIDS - OTHER CELLS
Biological fluids…………………….
Mesothelial cells…………….
Macrophages…………………………
Other cell types……………………….
Malignant cells…………………..
Lupus erythelatosus cells……………………...
Oral mucosa and upper respiratory tract cells………….
Cutaneous epithelial cells………………………………………………….
Vascular endothelialcells………………………………………………………
Stromal cells………………………………………………………………
REFERENCES………………………………………………………………………...
INDEX…………………………………………………
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