Cambridge University Press 978-1-108-48898-3 — Neonatal Hematology 3rd Edition Excerpt More Information Section I Developmental Hematology Chapter A Historical Review 1 Howard A. Pearson Ancient concepts of the blood were described by red in color ...These particles are so minute that Hippocrates and Galen 2000 years ago in their 100 of them placed side by side would not equal doctrine of “humors.” It was believed that the the diameter of a common grain of sand. body was made up of four humors – blood, In the centuries following, the development of phlegm, black bile, and yellow bile – and that compound microscopes with two lenses greatly these four components had the qualities of heat increased magnification and minimized spherical (hot-blooded!), cold, moist, and dry. The Galenic aberration, permitting more accurate descriptions concept of the blood prevailed through the Middle of the blood cells. Dr. William Hewson, who has Ages. Health or disease were a result of an imbal- been designated as one of the “fathers of hematol- ance, between these humors. This was the basis of ogy,” noted that the red cells were flat rather than the practice of therapeutic bloodletting (which, globular and also described the leukocytes for the fortunately, was performed infrequently on chil- first time [3]. The last of the formed elements of dren) through the mid nineteenth century as the blood, the platelet, was recognized indepen- a way to rid the body of the imbalance of humors dently by several investigators. The most defini- believed to cause a wide variety of diseases. tive early work on the platelet was done by Giulio The hematology of the fetus and newborn is Bizzozero. His monograph, published in 1882, a relatively recent area of study whose develop- clearly recognized these cells as being distinct ment depended upon the evolution of the science from red and white blood cells, and suggested of hematology and, especially, upon methods to that they should be called Blutplättchen. He also study the blood and its elements. As Wintrobe has assigned a hemostatic function to the platelet [4]. pointed out, the development of the field of hema- Dr. William Osler, early in his illustrious career, tology has been driven by technology. He divided also described platelets accurately, although he the evolution of hematology into two general believed that they may be infectious agents, per- areas: morphology, which relied on the develop- haps analogous to bacteria [5]. ment of microscopy, and quantitation of the ele- With improvements in microscopy, the mor- ments of the blood, which came later [1]. phology of the fixed blood cells began to be exam- The invention of the microscope enabled iden- ined using thin films of blood, spread and dried on tification of the blood cells. Antonie van glass slides, which were then stained with aniline Leeuwenhoek, working in Delft, Holland, con- dyes that stained differentially the nuclei and structed a primitive microscope from the minute granules of the leukocytes. Staining of peripheral biconcave lens mounted between two metal plates blood smears was developed by Paul Ehrlich in attached to a screw that permitted focusing. 1877, while he was still a medical student [6], and Leeuwenhoek’s publication in 1674 contained became practical in the early twentieth century by the first accurate description of the red blood the work of Dr. James Homer Wright of Boston, corpuscles [2]: who formulated the polychromatic Wright stain The blood is composed of exceedingly small par- that is still used today for morphologic examina- ticles, named globules, which in most animals are tion of the blood and bone marrow. The Neonatal Hematology, Pathogenesis, Diagnosis, and Management of Hematologic Problems, 3rd edition, ed. Pedro A. de Alarcón, Eric J. Werner, Robert D. Christensen, and Martha C. Sola-Visner. Published by Cambridge University Press. © Cambridge University Press 2021. 1 © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-108-48898-3 — Neonatal Hematology 3rd Edition Excerpt More Information A Historical Review development of supravital dyes provided Dr.L.EmmettHolt,The Diseases of Infancy and a method for assessment of erythropoiesis by reti- Childhood, first published in 1897, contained culocyte counts. These techniques permitted the a section on “the Diseases of the Newly-Born,” flowering of morphologic hematology, and many including the hemorrhagic disease, and a 17-page blood diseases such as the leukemias and the var- section on “the Diseases of the Blood,” which ious types of anemia were described on the basis included the normal blood findings in the newborn of typical morphological findings. [11]. Holt was obviously familiar with the many Hematology as a quantitative discipline began studies published in the German literature, and his with the development of practical and reliable meth- descriptions are reasonably consistent with modern ods to quantify accurately the numbers of the var- findings: ious blood cells. These methods used gridded chambers of uniform depth (hematocytometers) The percentage of hemoglobin is highest in the blood of the newly born ... At this time the into which precisely diluted suspensions of blood number of red blood corpuscles is from were placed. The numbers of cells in the chamber 4,350,000 to 6,500,000 in each cubic were counted and, when combined with the known millimeter ... In size, a much greater variation dilutions, the actual numbers of cells per cubic milli- is seen in the red cells of the neonate. In the blood liter in the patient’s blood could be calculated. of the foetus there are present nucleated red Hemoglobin levels were estimated by comparing corpuscles or erythroblasts. These diminish in the density of color in fixed dilutions of hemolyzed number toward the end of pregnancy. These are blood with colorometric standards and, later, by always found in the blood of prematures, but in spectroscopy. For many years, hemoglobin values infants born at term, they are seen only in small were reported as “%ofnormal”;andbecausethe numbers. The number of leukocytes in the blood definition of “normal” was often different there was of the newly born is three or four times that of the adult, being on the average 18,000 per cubic considerable variability from study to study. In millimeter. 1929, Dr. Maxwell Wintrobe described his method for obtaining the hematocrit or packed red-cell In 1921, Dr. W.P. Lucas and associates from the volume (PCV) by centrifugation of blood in a glass University of California Medical School in San tube [7]. He then defined so-called red-cell indices, Francisco described their extensive studies of the the mean corpuscular volume (MCV), mean cor- blood of 150 infants at birth and during the first 2 puscular hemoglobin (MCH), and mean corpuscu- months of life [12]. Their samples were obtained lar hemoglobin concentration (MCHC), which from serial punctures of the longitudinal sinus! proved of enormous value in classifying the various The polycythemia of the newborn and changes in forms of anemia [8]. The latest advance in blood-cell the leukocytes were defined clearly. quantitation began in the 1950s with the introduc- In 1924, Dr. H.S. Lippman from the University tion of increasingly more complicated and sophisti- of Minnesota published detailed studies of the cated computer-driven electronic instruments that blood of newborn infants [13]. He noted (without measure hemoglobin very accurately, the numbers further details) that “Denis published the first of all the blood cells, as well as the red-cell indices observations on the subject in 1831.” Lippman’s and the red-cell distribution width (RDW). Some review of the literature cited 70 previous articles instruments now also provide automated differen- on the hematology of the newborn. Most of these tial counts of the leukocytes. studies were published in European, especially Most of the pre-twentieth century American German, journals. Although there was consider- pediatric textbooks gave scant attention to hemato- able variability because of different methods and logic problems of the neonate. Dr. W.P. Dewees’s standards, the consensus of these early studies was 1825 A Treatise on the Physical and Medical that “Hemoglobin values at birth are higher than Treatment of Children, arguably the first American at any other period in the children’s life.” Some of pediatric textbook, and Dr. Job Lewis Smith’s1869 these studies described reticulocytosis and nor- A Treatise on the Diseases of Infancy and Childhood moblastemia in the first day of life, which declined gave only passing notice to blood conditions of the rapidly in the first week of life. Lippman con- neonate, such as neonatal jaundice and hemorrhage ducted serial studies of capillary blood over the from improper ligature of the umbilical cord [9, 10]. first 48 hours of life in 71 normal newborns as well However, the monumental pediatric text of as changes in the leukocytes during this period. 2 © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-108-48898-3 — Neonatal Hematology 3rd Edition Excerpt More Information A Historical Review It has been known for 100 years that the red- Roland Scott, using the relatively insensitive blood cells (RBC) of the fetus and newborn are “sickle cell prep,” demonstrated a much lower large compared with those of adults, as deter- frequency of “sicklemia” in black newborns than mined by microscopic measurement of red-cell was found in older children from the same com- diameter. Newer electronic cell-sizing techniques munity [22]. The development of techniques such have demonstrated that the mean MCV of the as acid agar gel electrophoresis and high pressure neonate’s red blood cells averages 110 fl, com- liquid chromatography have permitted genotypic pared with the 90 fl of adults.