Clinical hematology ...

Front matter

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Preface

This book, designed as a practical guide to the examination of the blood by methods adapted to routine clinical work, represents an endeavor to recount the salient facts of hematology as they are understood at the present time, to correlate certain of these facts with familiar pictures of disease, and to apply them to medical and surgical diagnosis. The purpose has been to interpret the blood report according to its true value as a clinical sign, neither exploiting it as a panacea for every diagnostic ill, nor belittling it because of its failure consistently to give the soughtfor clue in every instance.

A minimum amount of theoretical discussion has been introduced in the sections dealing with the physiology and pathology of the whole blood and of the cellular elements — only sufficient, in the author's judgment, to add clearness to a number of the mooted points of this science, which in its present transitional stage must still be regarded as one from which more or less hypothesis and conjecture are inseparable. Intimate familiarity with technique being an essential qualification for the comprehensive study of the blood, a somewhat lengthy consideration of this subject is given. The methods of examination likely to prove useful in every-day practice have been described in detail, perhaps sometimes at the risk of prolixity, in the hope of thus simplifying for the novice the minutiae of blood counting, staining, and other means of investigation. In the discussion of the primary anemias and of the anemias peculiar to infancy, prominent clinical features other than those referable to the blood have been briefly mentioned, in order to add clearness to the differential diagnosis. For convenience in reference, the various diseases included in the section on general hematology are arranged alphabetically, rather than grouped according to a traditional classification.

The greater part of the original data referred to in the text is taken from the records of the Pathological Institute of the German Hospital, where a systematic account of all blood examinations has been kept for the past six years. The remaining data represent the writer's personal examinations in hospital and private practice and in the army medical service, these sources of statistics together including about four thousand blood reports in various pathological conditions.

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PREFACE.

Hematological literature has been freely consulted in the preparation of this volume, special acknowledgment being due to Hayem, Ehrlich and Lazarus, von Limbeck, Rieder, Lowit, Turk, Grawitz, Cabot, Stengel, Thayer, Ewing, Taylor, and Coles for the profitable information gleaned from their writings. Due credit in the text has been given to these as well as to the other authors of whose labors use has been made.

The colored plates and other histological illustrations, the originals of which were made by Mr. E. F. Faber from fresh and stained specimens, bear evidence of the artist's technical skill and faithful attention to structural detail. Mr. S. Trenner has kindly furnished the engravings of several of the special instruments.

The author takes pleasure in acknowledging the assistance of his wife and critic in revising the proof of these pages ; in crediting Dr. G. P. Muller for collecting and verifying much statistical matter relating to hospital cases ; and in thanking Dr. J. Chalmers Da Costa and Dr. T. G. Ashton for helpful suggestions.

Introduction

The rapid growth and development of hematology during recent years and the practical application of many of its teachings to the diagnosis of various diseases have made this science one which no progressive medical man can afford to disregard. Examination of the blood gives definite clinical information which may be profitable both to the practitioner of internal medicine and to the surgeon, and the procedure is capable of throwing light upon the diagnosis in such a wide range of pathological conditions that it is difficult to single out any disease in which it may not be of some utility, either as positive or as negative evidence.

In the light of our present knowledge of the subject, clinical information of two different kinds may be derived from hematology, namely, findings which are pathognomonic of certain diseases ; and auxiliary data which, if considered in connection with other clinical manifestations, may prove either essential or helpful in establishing the precise nature of a disease.

Pathognomonic blood findings are unfortunately confined to a limited number of diseases : leukemia, the malarial fevers, relapsing fever, and filariasis. In pernicious anemia a typical picture is also found, if two conditions capable of exciting identical blood changes are excepted, the profound secondary anemias due to certain intestinal parasites and to nitrobenzol poisoning.

The blood examination affords data which, although not pathognomonic, are nevertheless essential for the diagnosis of chlorosis, Hodgkin's disease, splenic anemia, and secondary anemias dependent upon various causes. For example, in chlorosis a definite group of blood changes must exist in order to justify an unconditional diagnosis, although the occurrence of these changes, unassociated with other equally definite clinical signs, is insufficient evidence of this disease. In Hodgkin's disease, a condition indistinguishable from leukemia by an ordinary physical examination, the absence of a leukemic state of the blood at once excludes the latter disease. In the secondary anemias, it is obvious that the blood count alone can give the exact clue to the condition, by determining the degree and character of the blood impoverishment, and by tracing from time to time its progress.

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INTRODUCTION.

In this connection it is important to remember that pallor may go hand in hand with a normal hemoglobin percentage and erythrocyte value, and that on the other hand a high color by no means invariably signifies that the individual is not anemic. In addition to the diseases just named, hematology gives information which is often of great assistance in, although not essential for, the diagnosis of such conditions as enteric fever, sepsis, pneumonia, appendicitis, diabetes, syphilis, malignant disease, trichiniasis, and suppurative processes. Clinical experience has repeatedly illustrated the value of the serum reaction in typhoid and in Malta fevers, of Williamson's test in diabetes mellitus, of eosinophilia in trichiniasis, and of leucocytosis in sepsis, malignant neoplasms, suppurative lesions, and many of the acute infections.

Negative results from a blood examination also possess diagnostic value within certain limits, but too great reliance upon evidence of this sort more often proves delusive than helpful. In a patient whose waxy, yellowish facies suggests with equal force pernicious anemia, chronic nephritis, and, perhaps, liver cirrhosis, the absence of characteristic blood changes is sufficient to exclude the first-named condition. But failure to detect the malarial parasite does not necessarily exclude malarial fever ; a negative serum test does not absolutely rule out enteric fever ; and an absence of leucocytosis cannot be regarded as an infallible sign that a suppurative focus does not exist, nor does it always indicate the benignity of a neoplasm. Negative evidence, then, is usually to be considered merely suggestive, the real pertinence of the hint thus obtained depending upon its correlation with other physical signs and symptoms.

The significance of positive findings in bacteriological investigations of the blood is patent, and the conclusive value of this means of research in identifying obscure cases of general sepsis, malignant endocarditis, enteric fever, and plague, has been demonstrated in many instances. The conflicting and indifferent results which some investigators have obtained by this procedure were doubtless due largely to faulty technique, but these results promise to become more dependable and certain with the adoption or more exact technical methods.

At the present time the most useful information furnished by hematology has been derived from study of the cellular elements of the blood, but closer familiarity with the chemistry of this tissue, still an undeveloped science, will undoubtedly in the near future afford not only more tangible clues to the etiology and pathology of the blood diseases, but also will bring to light additional facts which may be applied to the diagnosis of these and

INTRODUCTION.

XI other maladies. The study of the coagulation time of the blood already promises to be of practical utility in the diagnosis and prognosis of cases of purpura, hemophilia, and jaundice, which are characterized by slow clotting and by a tendency toward hemorrhage.

The technique of blood examinations, such as described in the following pages, is neither elaborate nor difficult to master. Necessarily, it must be rigidly exact, but no more so than any other branch of physical diagnosis, if the worker is content only with the best results. To acquire a good working knowledge of hematology takes but a fraction of the time and application that one must spend in familiarizing one's self with the most common heart murmurs or chest signs, and the time thus spent equips the physician with an additional diagnostic agent of the greatest value. If the newly-graduated physician would provide himself with a microscope and a set of blood instruments, and systematically study the blood in the various general diseases which he encounters in practice, many a slip-shod diagnosis might be avoided, and a great stride forward made in popularizing this practical branch of clinical diagnosis.

Table Of Contents

INTRODUCTION

Section I. Examination Of The Blood By Clinical Methods

Page.

General Schema . 19

I. Examination of the Fresh Blood 19

Obtaining the Specimen 19

Preparing the Slide . • • • • • . 21

Microscopical Examination ....... 22

Changes Affecting the Erythrocytes • ■ • • • 22

Changes Affecting the Leucocytes 23

Increase of Fibrin, Blood Plaques, and Hemoconia . . 24

Blood Parasites ......... 24

Foreign Bodies . 24

II. Estimation of the Percentage of Hemoglobin • • 25

Von Fleischl's Hemometer . . . . . . . 25

Oliver's Hemoglobinometer . 32

Gowers' Hemoglobinometer ....... 34

Dare's Hemoglobinometer . 36

Tallquist's Method ........ 39

III. Counting the Erythrocytes and the Leucocytes . 40 Methods .......... 40

Diluting Fluids ......... 40

The Thoma-Zeiss Hemocytometer 42

Counting the Erythrocytes 45

Counting the Leucocytes ....... 49

Cleaning the Pipette ........ 52

Durham's Hemocytometer . . . . . . 52

Gowers' Hemocytometer ....... 54

Oliver's Hemocytometer ...... 56

IV. Microscopical Examination of the Stained Specimen e 58 Objects of Staining ........ 58

The Aniline Dyes ......... 59

Preparing the Films ........ 59

Fixation Methods . 61

Methods of Staining ........ 63

Ehrlich's Triacid Stain ........ 64

Jenner's Stain . 65

Prince's Stain 66 xiii

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TABLE OF CONTENTS.

Page.

Staining with Eosin and Methylene-blue .... 67

Staining with Eosin and Hematoxylin ..... 68

Staining with Thionin 69

Staining with Polychrome Methylene-blue .... 69

Differential Counting ........ 70

V. Counting the Blood Plaques 71

Determann's Method ........ 72

VI. Estimation of the Relative Volumes of Corpuscles and

Plasma . . 72

Daland's Hematocrit 73

Limitations of the Hematocrit ...... 74

VII. Estimation of the Specific Gravity .... 75 Hammerschlag's Method 75

VIII. Estimation of the Alkalinity ... . . . 77

Engel's Alkalimeter 77

IX. Determination of the Rapidity of Coagulation . 79

Glass Slide Method 80

Wright's Coagulometer . . . . . . . 80

X. Spectroscopics Examination . . . . . 81

The Sorby-Beck Microspectroscope 81

XI. Bacteriological Examination 83

Value of Positive Findings ....... 83

Methods . 83

Blood Cultures . 83

Staining Methods ........ 85

XII. Determination of the Serum Reaction ... 86

Widal's Test . 86

The Specific Test for Human Blood ..... 88

Section II. The Blood As A Whole

I. General Composition 93

Plasma, Serum, and Cells ....... 93

II. Color 94

Normal Variations ........ 94

Density and Opacity ........ 94

III. Odor and Viscosity ........ 95

IV. Reaction 95

Reaction in Health . . 95

TABLE OF CONTENTS. XV

Page.

Table of Normal Blood Alkalinity 96

Physiological Variations ....... 96

V. Specific Gravity 98

Normal Range . 98

Relation of Specific Gravity to Hemoglobin .... 99

Table of Hemoglobin Equivalents 100

VI. Fibrin and Coagulation 100

Relation of Fibrin to Coagulation . . • • . 100

Appearance of Fibrin in Fresh Blood • . • • . 101

Hyperinosis and Hypinosis ....... 102

Pathological Variations in Amount of Fibrin . . . • 102

VII. Oligemia 103

Permanent and Transient Polyemia • • • - • 104

Serous Plethora . . . . . . . . . 104

Cellular Plethora . 105

IX. Hydremia .105

Causes 105

X. Anhydremia 106

XI. Lipemia . . . 106

Amount of Fat in Normal Blood 106

Physiological and Pathological Lipemia 107

Tests for Fat . 107

XII. Melanemia . . 107

XIII. Glycemia . . . 108

Amount of Sugar in Normal Blood 108

Hyperglycemia . . 108

Test for Sugar . " 108

XIV. Uricacidemia . . . 109

Definition . . . . . . . . • / • io 9

Test for Uric Acid . 109 xvi

TABLE OF CONTENTS.

Page.

XV. Cholemia no

Definition . . no

Occurrence . . • • . • . . no

Test for Bile . . . • • . . . . no

XVI. Acetonemia and Lipacidemia . . • . . no

Definition .no

Occurrence . . • • • • . . no

Tests for Acetone and Fatty Acids ■ . . . . no

XVII. Bacteriemia . . .in

Latent Infection . 1 1 1

Blood Cultures . . . 112

Bacteria Found in the Blood 112

XVIII. Anemia .113

Pathogenesis . . . • . . . • . 115

Section III. Hemoglobin, Erythrocytes, Blood Plaques, And Hemoconia

General Properties • • • • • • . 119

Variations in Amount . • • • • . • . 121

Absolute Amount . 122

Hemoglobinemia . . . ... . . . 123

Carbon Monoxide Hemoglobin . . . • • . 125

II. Erythrocytes . 126

Histological Structure . . . . . . • . 127

Origin and Life History 128

Normal Number . 129

III. Influence of Physiological Factors on the Eryth-

rocytes . 130

Pregnancy, Menstruation, and Lactation . . . 131

Constitution and Nutrition 132

Digestion and Food . . . . . . . . 132

High Altitudes . . . . . . . . 133

TABLE OF CONTENTS. Xvii

Page.

IV. Pathological Changes in the Erythrocytes . • 134

Ameboid Motility 134

Alterations in Isotonicity 135

Hyperviscosity . . . • • • • • . 136

Deformities of Shape and Size • • ' • • . 136

Megalocytes . . . . • • . 136

Poikilocytes . • • • . • • 137

Endoglobular Degeneration . . . . . 138

Total Necrosis . . ....... 139

Atypical Staining Reaction . . . . • . . 140

Normoblasts 141

Megaloblasts 143

Atypical Erythroblasts . . . • • . . 146

Granular Degeneration . . . . . . . 147

Oligocythemia . .148

Polycythemia . . . . . . . . . 149

V. Blood Plaques . . 1 50

Histological Structure . . . . . . . . 150

Normal Number . 151

VI. Hemoconia 151

Histological Characteristics • • • • • • • 151

Section IV. The Leucocytes

I. General Characteristics 155

Ameboid Movement 156

Cell Granules . . . . • . . . . 157

Normal Number . . . . . . . . . 159

II. Classification . . . . . . . . . 159

Number and Percentage of Different Varieties • . . 159

Transitional Forms . . . . . . . . 162

Polynuclear Neutrophils 163

Basophile Cells 166

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TABLE OF CONTENTS.

Page.

Mononuclear Neutrophiles . . . • • • . 171

Neutrophilic Pseudolymphocytes 171

Reizungsformen . . . . . • • • . 171

Differential Table of the Leucocytes . . . . . 172

Origin and Development 173

Perinuclear Basophilia . . • . • • • • • l 7&

III. Leucocytosis .176

Classification of the Leucocytoses • • . • . . 177

Leucocytosis of the New-born . . • • . 178

Leucocytosis of Pregnancy and Parturition . . . 180

Leucocytosis Due to Thermal and Mechanical Influences 18 1

Terminal Leucocytosis 181

Degree of Increase 183

Functions . .184

Hypoleucocytosis and Hyperleucocytosis . . . 185

Inflammatory and Infectious Leucocytosis . . . 187

Leucocytosis of Malignant Disease . . . . 190

Post-hemorrhagic Leucocytosis . . . . . 191

Toxic Leucocytosis . . . . . . . 192

Experimental Leucocytosis . . . . . . 193

IV. Lymphocytosis 196

Physiological Lymphocytosis • . . . . . 197

Pathological Lymphocytosis . . . . . . . 197

Experimental Lymphocytosis • . . . . . 198

Clinical Significance . . . . . . .. 198

V. EOSINOPHILIA 198

Physiological Eosinophilia 199

Pathological Eosinophilia . . . . . . . 200

Experimental Eosinophilia . . . . . . . 201

Diminution in the Number of Eosinophiles .... 201

Clinical Significance 201

VI. Basophilia

TABLE OF CONTENTS. XIX

Page.

VII. MYELEMIA . * 202

VIII. Leucopenia 203

Physiological Leucopenia 204

Pathological Leucopenia 205

Experimental Leucopenia 207

Section V. Diseases Of The Blood

I. Chlorosis 209

Specifie Gravity 209

II. Pernicious Anemia 218

The Blood During Remissions . . . . . . 221

Megalocytosis . . . . . . . . . 221

Poikilocytosis . . . . . . . . . 223

Prevalence of Megaloblasts ....... 224

Polychromatophila . . . . . . . . 225

Granular Basophilia ........ 226

Pernicious Anemia and Severe Secondary Anemia • . 230

Pernicious Anemia and Chlorosis 230

Pernicious Anemia and Bothriocephalus Anemia • • . 231

Pernicious Anemia and Nitrobenzol Poisoning . . . 231

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Page.

III. Splenic Anemia 231

Splenic Anemia and Spleno-medullary Leukemia . . . 235

Splenic Anemia and Pernicious Anemia .... 235

Splenic Anemia and Hodgkin's Disease .... 235

Splenic Anemia and Splenic Tumors ..... 235

IV. Secondary Anemia 236

V. Post-hemorrhagic Anemia 239

Etiology 239

Immediate Effects of Hemorrhage ... . 240

Secondary Effects of Hemorrhage ...... 240

Degree of Blood Loss Compatible with Life .... 240

Regeneration of the Blood 241

Differential Table . . 243

VI. Leukemia 244

Relation of Erythrocyte and Leucocyte Counts . . 248

Nucleated Cells 248

Influence of Arsenic on the Leucocyte Count . . . 250

The Blood During Remissions . . . . . 251

TABLE OF CONTENTS. XXI

Page.

Acute Leukemia ......... 260

Influence of Intercurrent Infections 261

Spleno-medullary and Lymphatic Leukemia . 264

Leukemia and Pathological Leucocytosis .... 265

Leukemia and Lymphocytosis 265

Leukemia and Hodgkin's Disease 266

Leukemia and Tumors of the Spleen, Kidney, and Pancreas 266

Leukemia and Lymphatic Hyperplasia 266

VII. Hodgkin's Disease 267

Alkalinity, Specific Gravity, and Coagulation . • . 267

Nucleated and Deformed Cells 267

Hodgkin's Disease and Tuberculous Adenitis . . . 271

Hodgkin's Disease and Syphilitic Adenitis . . • . 271

Hodgkin's Disease and Local Lymphoma • • • • 271

Hodgkin's Disease and Lymphatic Sarcoma . . • . . . 271

Hodgkin's Disease and Lymphatic Carcinoma • • • 272

VIII. The Effect on the Blood of Splenectomy • • 272

Factors of the Blood Changes Following Splenectomy • • 274

Differential Table . . 275

Section VI. The Anemias Of Infancy And Childhood

I. Characteristics of the Blood in Children • • • 279

Fetal Blood 279

The Blood at Birth . . 280

II. Anemia in Children 282

General Characteristics . 283

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Page.

Primary Anemia . 284

Mild Anemia . 287

Severe Anemia ......... 287

Anemias with Leucocytosis • .. . . . 287

Etiology of Secondary Anemia 288

Anemia Due to Syphilis 288

Anemia Due to Rachitis 288

Anemia Due to Tuberculosis ...... 289

Anemia Due to Gastro-intestinal Diseases . . . 289

Post-typhoid Anemia 289

Anemia Infantum Pseudoleukemica .... 290

Bacteriemia in Children 292