What is hematology?

Science and Profession

Most branches of medical science study a particular organ that is made of specific tissues and is located in a definite part of the body. Hematology is unique because its subject, the blood, is a liquid tissue constantly in motion and therefore in constant contact with every other tissue and organ of the body.

It has been estimated that blood travels about sixteen kilometers (ten miles) per hour. It takes six seconds for blood to travel from the heart to the lungs, about eight seconds to travel from the heart to the brain, and only fourteen seconds to travel from the heart all the way to the toes. Hematologists studying these shifting currents of the blood are able to detect patterns that allow the early discovery of many disorders of the blood itself and of the organs that it supplies.

Blood is a complex material composed of approximately 55 percent plasma and 45 percent cells, which are also called formed elements. The plasma, or liquid portion of the blood, is about 90 percent water and 10 percent substances dissolved or suspended in that water. Part of that 10 percent consists of a remarkable array of substances, including nutrients, gases, salts, wastes, and hormones being transported around the body. The other, larger part of the 10 percent is another remarkable array: plasma proteins such as fibrinogen, albumin, and globulins with a great diversity of functions to accomplish. The modern hematologist’s ability to measure and monitor all these plasma components precisely has greatly aided physicians in the treatment of innumerable diseases.

Beyond an analysis of the ingredients of the plasma, hematologists focus on the normal and abnormal conditions of the blood’s cells. An individual has around twenty-five trillion red blood cells; ten million of these cells die or are destroyed each second, and two hundred billion new ones need to be made each day. Hematologists discovered that these tiny, biconcave discs packed with hemoglobin transport the vast majority of the oxygen constantly needed by every cell of every organ for energy production.

Before each red blood cell is released from the bone marrow where it is produced, the bulk of its living nucleus is expelled. A small amount of nuclear material remains as a fine network in these young cells, called reticulocytes. The number of reticulocytes released into the blood is an indication of the activity of the bone marrow. Hematologists use this number both to diagnose conditions such as anemia in its various forms and to assess the patient's response to treatment.

Not only the total number and maturity but also the shape, diameter, and flexibility of red blood cells can give the hematologist important information. For years, such information was gathered by laborious manual methods. Electronic counters can now obtain this information with great speed and even greater accuracy.

Hematologists can also gauge the effectiveness of red blood cells by seeing how much hemoglobin they contain. The amount of this red pigment present, and therefore functioning, was once estimated by being matched against progressively darker-colored glass “standards.” Now this figure too is accurately determined using a precise photoelectric technique.

Another useful test is called the packed cell volume (PCV) test. It not only reveals the proportion of the red blood cells to the plasma but also allows the calculation of those cells' average size and hemoglobin content.

An equally common blood investigation is the erythrocyte sedimentation rate (ESR). The erythrocytes, the term that hematologists use to describe red blood cells, normally fall slowly down through the plasma in a standard tube. A very rapid sedimentation rate demonstrates a disturbance in the plasma proteins that may be very dangerous. Usually, the faster the erythrocytes settle out, the sicker the patient, with a wide variety of inflammations as possible causes.

Beginning in the mid-twentieth century, an increasing number of radioactive tests were developed by which hematologists could more accurately assess total blood volume and the survival time of red blood cells or platelets in circulation. Assessing total volume is important. A loss of more than one liter (two pints) is quite dangerous because it can cause a total collapse of the blood vessels.

This reaction gives a clue about the importance of a second kind of blood cell, the platelet, and its work in stopping bleeding. When a blood vessel is first cut, platelets (or thrombocytes) rush to the site. They swell into irregular shapes, become sticky, and clog the cut, creating a plug. The smallest blood vessels rupture hundreds of times a day, and platelets alone are able to make the necessary repairs. If the cut is too large, then platelets, which are like sponges filled with diverse and biologically active compounds, disintegrate. Their ingredients react with numerous clotting factors in the plasma to initiate clot formation.

Hematologists check blood samples carefully to ascertain whether their patients possess the normal number of platelets—more than a trillion for the average adult. Since platelets live only about ten days, it is necessary to monitor those patients who exhibit significantly low amounts of these cells. If their bone marrow is not constantly replacing these platelets, these patients might bleed to death from a small cut. Doctors must also monitor any tendency toward the formation of too many platelets, as this can lead to thrombophlebitis, the blockage of a vein by a blood clot.

As with red blood cells, the widespread use of electronic counters has made the measurement of the numbers of platelets and of white blood cells (the third type of blood cell) rapid, efficient, and extremely accurate.

White blood cells are hardest to count because they are the least numerous, making up only 0.1 percent of the total blood. Their number also varies dramatically, from four thousand to eleven thousand per cubic centimeter of blood, according to the individual, the time of day, the outside temperature, and many other ordinary factors.

Hematologists can deduce the degree of maturity of circulating white blood cells from the appearance of their nuclei. There are five kinds of white blood cells (or leukocytes), whose normal proportions in the blood are quite specific and change drastically if an infection is present. The number of monocytes, for example, is normally 5 percent of the total number of white blood cells. If typhus, tuberculosis, or Rocky Mountain spotted fever organisms are present, that number will rise to 20 or 30 percent. The normal 60 percentage of neutrophils will increase to 75 percent or more in the presence of pneumonia or appendicitis.

Diagnostic and Treatment Techniques

Blood to be tested by a hematologist is withdrawn from a vein. A thin smear or film of the blood is placed on a glass slide and stained to bring out identifying features more prominently. The microscope then reveals the proportion of different cell types and any variation from the normally expected amount. This examination alone may give an immediate diagnosis of a particular blood disorder. For example, a red blood cell count that is less than four million or more than six million per cubic centimeter of blood is considered unusual and is probably an indication of disease.

It often becomes necessary to study not only the circulating blood cells but also the original cells within the bone marrow that produce the erythrocytes, thrombocytes, and leukocytes. To do so, the hematologist must use a long, thin needle to remove a sample of the marrow from within the tibia (shinbone) of a child or the pelvis (hipbone) or sternum (breastbone) of an adult. This test can provide a reliable diagnosis of a specific blood disorder.

The blood disorders that hematologists are routinely called on to diagnose and treat include diseases of the red blood cells, white blood cells, platelets, and clotting factors and failures of correct blood formation.

Disorders involving a deficiency of red blood cells or their hemoglobin are called anemias. There are many types of anemia, which are named, distinguished, and treated according to their causes. Some anemias exist because of a lack of the materials needed to build red blood cells: iron, vitamin B12, and folic acid. Other anemias are caused by a shortening of the life span of red blood cells or by inherited abnormalities in hemoglobin. Still others are attributable to chronic infections or cancer.

Iron-deficiency anemia is by far the most common; it is particularly prevalent in women of childbearing age and in children. In young children who are growing rapidly, constant increase in muscle mass and blood volume will cause anemia unless a high enough level of iron is present in the diet. All women between puberty and the menopause lose iron with the menstrual flow of blood and, therefore, are always prone to iron-deficiency anemia. A pregnant woman is even more likely to develop this condition, as iron is literally removed from her body and transferred through the placenta to the developing fetus.

The symptoms of iron-deficiency anemia may include a reduced capacity for physical work, paleness, breathlessness, increased pulse, and possibly a sore tongue. The hematologist witnessing small, misshapen red blood cells deficient in hemoglobin will recommend an increase in iron in the diet. The hematologist will also send the patient for various gastrointestinal tests because of the possibility of internal bleeding or failure of the intestine to absorb iron properly.

Another class of anemias involves a lack of vitamin B12 or folic acid. Without the help of these two substances, the bone marrow cannot build red blood cells correctly. Folic-acid deficiency anemias are diagnosed when the hematologist finds bizarre cells called megaloblasts in the patient’s bone marrow. Both vitamin B12 and folic acid can be added to the diet or given by injection. The problem may stem, however, not from an insufficient amount of vitamin B12 in the diet but from the inability of the stomach lining to produce a substance called intrinsic factor. In this case, the patient will never be able to absorb the vitamin properly and is said to suffer from pernicious anemia.

Those anemias characterized by the early and too-frequent destruction of red blood cells are grouped together as hemolytic anemias. Some of these disorders are acquired, while others are inherited. In both types, hemoglobin from the destroyed red blood cells can be detected by the hematologist in the plasma, the urine, or the skin, where it causes the yellowing called jaundice.

Because the many types of anemia are so common, hematologists find that the diagnosis and treatment of these diseases form a large part of their everyday practice. All types of leukemia, on the other hand, are quite rare. They are caused by a change in one kind of primitive blood cell in the bone marrow. The result is uncontrolled growth of these cells, which do not mature but rather invade the blood as badly functioning cells. Leukemia is often thought of as cancer of the blood.

Although it is not known what causes leukemia in a particular person, the disease seems to be associated with certain factors, including injury by chemicals or radiation, viruses, and genetic predisposition. Many cases of acute leukemia occur in either children under fourteen or adults between fifty-five and seventy-five years of age. In children, it is almost always a disorder in the bone-marrow cells that produce the white blood cells, called lymphocytes. This disorder is called acute lymphoblastic leukemia, or ALL. Adult leukemia usually occurs in the bone marrow that forms some other type of white blood cell and is called acute nonlymphoblastic leukemia, or ANLL (also known as acute myelocytic leukemia, or AML).

Hematologists diagnose both conditions by their shared symptoms: abnormal bone-marrow tissue and a lack of normal white blood cells and platelets in the circulating blood. The patient will often have been referred to the hematologist because of an uncontrollable infection (due to lack of normal white blood cells) or uncontrollable bleeding (due to lack of normal platelets). In both children and adults, anemia usually accompanies acute leukemia because defective bone marrow is not able to produce red blood cells properly either.

Less rare than acute leukemia are the various chronic types. One type, called chronic granulocytic leukemia (CGL) (also chronic myeloid leukemia or CML), occurs most often after the age of fifty. Unfortunately, its early symptoms are few and vague, so that the disease may have progressed greatly before its presence is even suspected. By such time, an enormous enlargement of the spleen, along with elevations in both white blood cell and platelet counts, can be noted.

Two stages are usually seen in chronic granulocytic leukemia. Early treatment can relieve all symptoms, shrink the spleen, and return all blood cells to normal values. Eventually, however, the leukemic condition recurs, and the patient usually lives an average of only three years. Bone marrow transplantation from a suitable donor and a more recent process in which one’s own marrow is removed, irradiated, and returned to the bones have increasingly become the recommended treatments for this condition.

A second type of chronic leukemia is known as chronic lymphatic leukemia (CLL). Unlike most of the other leukemias, CLL has no known cause, but it is most often found in male patients over the age of forty. Often quite symptomless, it is only discovered by chance. The hematologist is able to diagnose CLL by an increased proportion of abnormal white blood cells present in the blood. Surprisingly, this form of leukemia can vary from a case that remains symptomless, with the patient surviving twenty years or more, to a rapidly progressing case with increasing anemia and constant infections.

The third major class of disorders diagnosed and treated by hematologists consists of those involving abnormal bleeding
. The diagnosis is quite simple. The hematologist notes whether bleeding from a tiny puncture in the ear lobe stops within three minutes, as it should. If the bleeding does not stop, the determination of the cause may be difficult; it may involve too few platelets or abnormal or missing clotting factors.

Very precise tests of an increasingly sophisticated nature are now used by hematologists to determine whether a bleeding disorder is attributable to inheritance (as with hemophilia), a vitamin K deficiency, or a side effect of medication or is secondary to a type of leukemia.

Perspective and Prospects

That blood and the vessels that carry it are important to life and health was evident even to ancient peoples. Around 500 BCE, Alcmaeon of Croton, a Greek philosopher and medical theorist, was the first to discover that arteries and veins are different types of vessels. A century later, Hippocrates observed that blood, left to stand, settles into three distinct layers. The top layer, the largest, is a clear, straw-colored liquid that is now called plasma. The middle layer is a narrow white band that is now known to contain white blood cells. The bottom, quite large layer contains the cells that are now called red blood cells.

Very little else of value seems to have been learned about the blood until the seventeenth century, which witnessed many discoveries in medical science. In 1628, William Harvey, an English doctor, demonstrated scientific evidence of circulation. He found proof of a circular route and of the purpose of circulation. By 1661, the Italian scientist Marcello Malpighi reported seeing the tiny vessels called capillaries in the lungs of a frog.

Another giant step toward modern hematology occurred in the 1660s due to the efforts of Richard Lower of England and Jean-Baptiste Denis of France. Almost simultaneously, they accomplished blood transfusions from dog to dog and, soon after, from animal to human. Some transfusions were very successful; others were fatal to the patient. Almost 250 years would pass before the reason for success or failure would be learned.

In 1688, the Dutch scientist Antoni van Leeuwenhoek was able to describe and measure red blood cells accurately. He also observed that they changed shape to squeeze through tiny blood vessels. It was almost a hundred years later, in the 1770s, that Englishman Joseph Priestley found that the oxygen in the air changed dark blood from the veins into a bright red color. Only in the 1850s did the German researcher Otto Funke find within those red blood cells the compound hemoglobin, which is affected by the presence or absence of oxygen.

Although the first research on blood clotting was done by William Hewson in 1768, the disease called hemophilia, or the failure of the blood to clot, was not described until 1803, by John Otto.

In the United States in the early twentieth century, Karl Landsteiner discovered why certain blood can be safely transfused: the existence of the ABO blood types. This renowned hematologist was still advancing his science forty years later when he discovered the Rh system of blood types.

Another renowned hematologist, Max Perutz, worked steadily from 1939 to 1978 to understand fully the structure and function of the hemoglobin molecule. The 1940s had seen another breakthrough when Edwin Cohn, another American, discovered how to separate and purify the various plasma proteins. His work gave fellow hematologists the tools to study individual plasma components in order to learn the exact role of each in the blood. Since that time, scores of hematologists have so advanced this medical science that blood seems to have yielded most of its secrets. The ability of hematologists to treat so many types of anemia, leukemia, and other blood disorders successfully is the fruit of their tireless work.

Bibliography

American Society of Hematology. http://www.hematology.org

Avraham, Regina. The Circulatory System. Philadelphia: Chelsea House, 1989.

Bick, Roger L. Disorders of Thrombosis and Hemostasis: Clinical and Laboratory Practice. 3d ed. Philadelphia: Lippincott Williams & Wilkins, 2002.

Eads, Jennifer R., Neal J. Meropol, and Jerry L. Spivak. "Update in Hematology and Oncology: Evidence Published in 2012." Annals of Internal Medicine 158, no. 10 (May 2013): 755–760.

Hoffman, Ronald, et al., eds. Hematology: Basic Principles and Practice. 6th ed. Philadelphia: Saunders/Elsevier, 2013.

Kaushansky, Kenneth, et al., eds. Williams Hematology. 8th ed. New York: McGraw-Hill, 2010.

Rodak, Bernadette F., George A. Fritsma, and Elaine M. Keohane, eds. Hematology: Clinical Principles and Applications. 4th ed. St. Louis, Mo.: Saunders/Elsevier, 2012.

Tortora, Gerard J., and Bryan Derrickson. Introduction to the Human Body: The Essentials of Anatomy and Physiology. 9th ed. Hoboken, N.J.: John Wiley & Sons, 2012.